Increasing Your Resistance to Infection

[1] Irwin M,Mascovich A,Gillin JC,Willoughby R,Pike J,Smith TL. "Partial sleep deprivation reduces natural killer cell activity in humans." Psychosomatic Medicine. 1994 Nov-Dec;56:493-8. (Issue number 6) Research reported byDepartment of Psychiatry, University of California, San Diego 92161.. =6678= = Author's abstract: Sleep disturbance, measured by either subjective report or electroencephalographic (EEG) assessment of sleep, correlates with a reduction of natural killer (NK) cell activity in major depression. To test whether sleep loss independent of mood disturbance alters daytime values of cellular immune function, the effect of late-night partial sleep deprivation on NK cell activity was studied in 23 medically and psychiatrically healthy male volunteers. After a night of sleep deprivation between 3 and 7 AM, NK cell activity was reduced in 18 of the 23 subjects with average lytic activity reduced significantly (p < .01) to a level 72% of the mean of three separate baseline values. After a night of resumed nocturnal sleep, NK cell activity had returned to baseline levels. These data implicate sleep in the modulation of natural immunity and demonstrate that even modest disturbances of sleep produce a reduction of NKcell activity.

[2] Nash MS. "Exercise and immunology." Med Sci Sports Exerc. 1994 Feb;26:125-7. (Issue number 2) according to PMU 1994 Jun Research reported by Department of Orthopaedics and Rehabilitation, University of Miami School of Medicine, Coral Gables, FL 33146.. =5142= = Author's abstract: The documented effects of physical activity on host defense date to the early 1900s, although the influences of exercise on infectious and neoplastic disease susceptibility in healthy persons have long been subject to widespread disagreement. Even less is known of the effects of exercise in reducing illness predilection for persons already susceptible to, or afflicted by, immune disease or dysfunction. Recently, however, reports suggest that exercise may reduce the incidence and severity of infection. These reports have been bolstered by well-conducted epidemiologic and laboratory studies demonstrating a link between moderate exercise and either heightened immune function or reduced disease incidence, a relationship that is reversed in instances of immoderate exercise. This symposium will present current information addressing beneficial and detrimental influences of exercise on immune function and disease susceptibility. The authors will emphasize direct effects of acute exercise and physical training on immune cells and their neuroendocrine/immune modulators. The relationship among exercise, infection susceptibility, and immune system function will be highlighted, as well as exercise-induced activation of, and illness/disease regulation by, natural killer cells. Consequences of exercise on immune function and disease advancement will be addressed for persons with neoplasia, autonomic dysfunction, aging-related immunosenescence, and AIDS.

Nieman DC,Henson DA. "Role of endurance exercise in immune senescence." Med Sci Sports Exerc. 1994 Feb;26:172-81. (Issue number 2) according to PMU 1994 Jun Research reported by Department of Health, Leisure, and Exercise Science, Appalachian State University, Boone, NC 28608.. =5143= = Author's abstract: The immune system undergoes significant changes with advancing age. The increased incidence of malignancy, infectious disease, and autoimmune disorders with age is felt to be linked with this decline of immunocompetence. The aging process does not uniformly affect the immune system, however, and there is a high degree of individual variation. There is growing evidence that the variation in immune function among the elderly is associated at least in part withenvironmental factors such as nutritional status and physical activity. Although investigation of the relationship between endurance exercise and immune function in elderly subjects has just recently begun, data from the few studies available are intriguing and have potential for widespread public health influence. These data are reviewed in this paper, with directions given for future research.

[3] Steele RW,Charlton RK. "Immune modulators as antiviral agents." Clin Lab Med. 1987 Dec;7:911-24. (Issue number 4) Research reported by Pediatric Transplantation Center, University of Arkansas for Medical Sciences, Little Rock.. =9540= = Author's abstract: Immune modulators have exhibited some limited efficacy in the prevention or treatment of viral infection. Such agents have included transfer factor, thymosin, thymic humoral factors, levamisole, isoprinosine, immune RNA, young lymphocytes, vitamin C, and BCG. This article focuses on data that have examined clinical application of immune adjuvant therapy.

[4] McMurray DN. "Cell-mediated immunity in nutritional deficiency." Prog Food Nutr Sci. 1984;8:193-228. (Issue number 3-4) =9581= = Author's abstract: Dietary deficiencies of specific nutrients profoundly alter cell-mediated immune responses in man and experimental animals. Both moderate and severe deficiencies are associated with significant changes in immunocompetence. Diets with inadequate levels of protein, calories, vitamin A, pyridoxine, biotin and zinc result in loss of thymic cellularity. Secondary to thymic atrophy, the production of thymic hormones critical for the differentiation of T lymphocytes is reduced, especially in protein-calorie malnutrition and zinc deficiency. Confirmation of a T cell maturational defect in nutritional deprivation comes from the observations of decreased total (T3 and rosette-forming) T cells in the peripheral blood of children with kwashiorkor and marasmus, with preferential loss of helper/inducer (T4) T cell subsets. Reduced number and in vitro function of T cells have also been reported in experimental deficiencies of iron, zinc, copper, and vitamins A and E. Loss of cutaneous hypersensitivity to mitogens and antigens is a consistent sequela of dietary deficiencies of protein, vitamins A and C, pyridoxine, iron and zinc. Cell-mediated immunity directed against allogeneic histocompatibility antigens (e.g. mixed leukocyte cultures, graft versus host, skin graft rejection) may actually be enhanced by experimental protein and polyunsaturated fat deficiencies. Alternatively, pyridoxine, ascorbate and biotin deficiencies resulted in delayed rejection of skin allografts. Cytotoxic T lymphocyte (CTL) activity is impaired in zinc-, iron- and copper-deficient mice, as well as in scorbutic guinea pigs. Natural killer (NK) cell function may be either enhanced or depressed, depending upon the nutrient and its effects on interferon production. Several authors have demonstrated normal or enhanced macrophage activity in a variety of experimental deficiencies. The extrapolation of these observations to infectious disease resistance is not straightforward, and depends upon the nature of the microbe, its own nutrient needs, and the relative importance of innate, as opposed to immunologic, defense mechanisms.

[5] Jefferies WM. "Cortisol and immunity." Medical Hypotheses. 1991 Mar;34:198-208. (Issue number 3) =8224= = Author's abstract: The relationship between adrenocortical function and immunity is a complex one. In addition to the well-known detrimental effects of large, pharmacologic dosages of glucocorticoids upon the immune process, there is impressive evidence that physiologic amounts of cortisol, the chief glucocorticoid normally produced by the human adrenal cortex, is necessary for the development and maintenance of normal immunity. This evidence is reviewed, and the importance of differentiating between physiologic and pharmacologic dosages and effects is discussed. The popular use of synthetic derivatives of cortisol, which differ greatly from the natural hormone in strength, and the dynamic nature of the normal adrenocortical response, which varies with the degree of stress being experienced, have contributed to the confusion. Further studies of the nature of the beneficial effect of cortisol, and possibly of other normal adrenocortical hormones, upon immunity in humans are needed, especially in view of recent evidence of a feedback relationship between the immune system and the hypothalamic-pituitary-adrenal axis, and with the increasing awareness not only that the immune process provides protection against infection, but also that its impairment seems to be involved in the development of autoimmune disorders, malignancies and the acquired immunodeficiency syndrome (AIDS).

[6] Nuwayri-Salti N,Murad T. "Immunologic and anti-immunosuppressive effects of vitamin A." Pharmacology. 1985;30:181-7. (Issue number 4) =2969= = Author's abstract: The effects of vitamin A alcohol on cell-mediated immunity in vitro and its ability to prevent the immunosuppressive effects of prednisolone and cyclophosphamide in vivo were studied in mice. Lymphocytes from Calmette-Guerin bacillus (BCG) sensitized mice were stimulated specifically with purified protein derivative (PPD) and nonspecifically with phytohemagglutinin (PHA). In the vitamin A injected animals there was significant enhancement of the spleen lymphocyte transformation not only in the PPD-sensitive cells but also in the T cells at large. In addition, vitamin A was able to restore to normal the cellular and humoral forms of immunity in prednisolone and cyclophosphamide-treated animals. It is suggested that vitamin A in nontoxic doses may have a role in enhancing the responses to weak immunogens and in reversing immunosuppression.

[7] Yen SS,Morales AJ,Khorram O. "Replacement of DHEA in aging men and women. Potential remedial effects." Annals of the New York Academy of Sciences. 1995 Dec 29;774:128-42. according to Thorne web May 14, 1996 Research reported by Department of Reproductive Medicine, University of California, San Diego, La Jolla 92093, USA.. =9105= = Author's abstract: DHEA in appropriate replacement doses appears to have remedial effects with respect to its ability to induce an anabolic growth factor, increase muscle strength and lean body mass, activate immune function, and enhance quality of life in aging men and women, with no significant adverse effects. Further studies are needed to confirm and extend our current results, particularly the gender differences.

[8] Alexander M,Newmark H,Miller RG. "Oral beta-carotene can increase the number of OKT4+ cells in human blood." Immunol Lett. 1985;9:221-4. (Issue number 4) =3677= = Author's abstract: Oral doses of beta-carotene (180 mg/day) given for 2 wk to normal human volunteers significantly increased the frequency of OKT4+ (helper/inducer T cells) after 7 days and of OKT3+ (all T cells) after 14 days. The frequency of OKT8+ cells was unaffected, as compared to untreated controls. Plasma levels of beta-carotene were markedly elevated throughout the study. Plasma levels of vitamin A were slightly (but significantly) elevated on days 7 and 14. No toxicity was observed. Oral beta-carotene treatment may be a clinically effective means of enhancing T4+ lymphocytes.

[9] Hussey GD,Klein M. "A randomized, controlled trial of vitamin A in children with severe measles." New England Journal of Medicine. 1990 Jul 19;323:160-4. (Issue number 3) Comment in N Engl J Med 1990 Dec 20;323(25):1774-5 Copy in office. 92021901 =2712= Oral water-miscible retinyl palmitate 400,000 units daily for two days. = Conclusion: Treatment with vitamin A reduces morbidity and mortality in measles, and all children with severe measles should be given vitamin A supplements, whether or not they are thought to have a nutritional deficiency. = Author's abstract: BACKGROUND. Measles kills about 2 million children annually, and there is no specific therapy for the disease. It has been suggested that vitamin A may be of benefit in the treatment of measles. METHODS. We conducted a randomized, double-blind trial involving 189 children who were hospitalized at a regional center in South Africa because of measles complicated by pneumonia, diarrhea, or croup. The children (median age, 10 months) were assigned to receive either vitamin A (total dose, 400,000 IU of retinyl palmitate, given orally; n = 92) or placebo (n = 97), beginning within five days of the onset of the rash. At base line, the characteristics of the two groups were similar. RESULTS. Although clinically apparent vitamin A deficiency is rare in this population, the children's serum retinol levels were markedly depressed (mean [+/- SEM], 0.405 +/- 0.021 mumols per liter [11.6 +/- 0.6 micrograms per deciliter]), and 92 percent of them had hyporetinemia (serum retinol level less than 0.7 mumols per liter [20 micrograms per deciliter]). Serum concentrations of retinol-binding protein (mean, 30.1 +/- 2.0 mg per liter) and albumin (mean, 33.4 +/- 0.5 g per liter) were also low. As compared with the placebo group, the children who received vitamin A recovered more rapidly from pneumonia (mean, 6.3 vs. 12.4 days, respectively; P less than 0.001) and diarrhea (mean, 5.6 vs. 8.5 days; P less than 0.001), had less croup (13 vs. 27 cases; P = 0.03), and spent fewer days in the hospital (mean, 10.6 vs. 14.8 days; P = 0.01). Of the 12 children who died, 10 were among those given placebo (P = 0.05). For the group treated with vitamin A, the risk of death or a major complication during the hospital stay was half that of the control group (relative risk, 0.51; 95 percent confidence interval, 0.35 to 0.74).

[10] Coutsoudis A,Broughton M,Coovadia HM. "Vitamin A supplementation reduces measles morbidity in young African children: a randomized, placebo-controlled, double-blind trial." American Journal of Clinical Nutrition. 1991 Nov;54:890-5. (Issue number 5) Research reported by Department of Paediatrics and Child Health, University of Natal, Durban, South Africa.. =3809= = Author's abstract: The effects of vitamin A supplementation on measles morbidity are unclear. Sixty hospitalized children aged 4-24 mo with complicated measles received a World Health Organization--(WHO) recommended dose of vitamin A or placebo. The two groups were comparable in known covariants of measles severity: weight-for-age percentiles, overcrowding, rash, total lymphocytes, and serum concentrations of zinc, albumin, prealbumin, retinol-binding protein, and vitamins A and E. Ninety percent of the patients had hyporetinemia. Integrated morbidity scores, determined by severity of condition (eg, diarrhoea, herpes, and respiratory-tract infection) were assigned on day 8 and 6 wk and 6 mo; these were reduced by 82%, 61%, and 85%, respectively, in the supplemented group, which was mainly due to reduced respiratory-tract infection. There was one death in the placebo group. At 6 wk weight gain was significant in the supplemented group. Despite the selected sample, attention to multiple covariates enhances the validity of the data obtained and supports the current WHO recommendations for vitamin A supplementation during measles.

Fawzi WW,Chalmers TC,Herrera MG,others. "Vitamin A supplementation and child mortality. A meta-analysis." Journal of the American Medical Association. 1993 Feb 17;269:898-903. (Issue number 7) (Copy available). =2284= = Conclusion: -Vitamin A supplements are associated with a significant reduction in mortality when given periodically to children at the community level. Factors that affect the bioavailability of large doses of Vitamin A need to be studied further. Vitamin A supplements should be given to all measles patients in developing countries whether or not they have symptoms of vitamin A deficiency. = Author's abstract: OBJECTIVE--A two-part meta-analysis of studies examining the relationship of vitamin A supplementation and child mortality. DATA SOURCES--We identified studies by searching the MEDLARS database from 1966 through 1992 and by scanning Current Contents and bibliographies of pertinent articles. STUDY SELECTION--All 12 vitamin A controlled trials with data on mortality identified in the search were used in the analysis. DATA EXTRACTION--Data were independently extracted by two investigators who also assessed the quality of each study using a previously described method. DATA SYNTHESIS--We formally tested for heterogeneity across studies. We pooled studies using the Mantel-Haenszel and the DerSimonian and Laird methods and adjusted for the effect of cluster assignment of treatment groups in community-based studies. Vitamin A supplementation to hospitalized measles patients was highly protective against mortality (DerSimonian and Laird odds ratio, 0.39; 95% confidence interval, 0.22 to 0.66; P = .0004) (part 1 of the meta-analysis). Supplementation was also protective against overall mortality in community-based studies (DerSimonian and Laird odds ratio, 0.70; clustering-adjusted 95% confidence interval, 0.56 to 0.87; P = .001) (part 2 of the meta-analysis).

Rumore MM. "Vitamin A as an immunomodulating agent" Clin Pharm. 1993;12:506-514. Author's abstract: Findings on the benefits and mechanism of action of vitamin A in measles and other infectious diseases and immunocompromised states are discussed. Vitamin A deficiency is one of the world's major malnutrition problems and is most commonly found in children under the age of five years. An association between vitamin A status and immune function has been suggested by community studies and animal experiments. Mortality and susceptibility to infection and diarrhea are higher in children with vitamin A deficiency. The association between increased mortality and morbidity and vitamin A deficiency is strongest in children with measles. Vitamin A supplementation reduces mortality and complications resulting from measles. Measles may increase the body's utilization of vitamin A, possibly because of the rapid destruction of epithelial surfaces. Vitamin A may boost immune responses in the elderly, persons with high exposure to ultraviolet light, patients who have undergone surgery, and persons with parasitic infection, but more studies are needed. The immune defect caused by vitamin A deficiency may be due to alterations in the glycoproteins of the lymphocyte membrane, an adverse effect on helper T-cell function, the effect on epithelial tissue, or some other mechanism. Vitamin A therapy is relatively safe, and its effectiveness in children with measles and possibly other groups appears to justify public health campaigns to eliminate vitamin A deficiency. Vitamin A apparently has important immunomodulating properties, notably in patients with measles.

[11] Neuzil KM,et al. "Safety and pharmacokinetics of vitamin A therapy for infants with respiratory syncytial virus infections" Antimicrobial Agents and Chemotherapy. 1995;39:1191-1193. Vitamin A therapy for infants: Acute viral infections in children are associated with low serum vitamin A levels. The magnitude of the reduction is related to the severity of the illness. Acute administration of high doses of vitamin A has been shown to reduce mortality in children with measles. As a result, short-term vitamin A therapy should be considered for other viral illnesses. While 200,000 IU has been given safely over a 24-hour period to children 6-24 months of age with measles, its safety is less certain in infants less than 6 months of age. Administration of 50-100,000 IU of oil-based vitamin A to infants has been reported to cause vomiting and bulging of the fontanelle. The present study suggests that lower doses, such as 25-50,000 units, are safe for this younger age group. Until additional toxicity studies are done, vitamin A should be given for one day only, in two divided doses.

[12] Anderson R,Oosthuizen R,Maritz R,Theron A,Van Rensburg AJ. "The effects of increasing weekly doses of ascorbate on certain cellular and humoral immune functions in normal volunteers." American Journal of Clinical Nutrition. 1980 Jan;33:71-6. (Issue number 1) Copy in office. 97121302 =10894= = Author's abstract: Certain functions of the blood neutrophils and lymphocytes from normal adult volunteers were evaluated after the ingestion of increasing doses of ascorbate. Serum immunoglobulins and levels of C'3 and total hemolytic complement were also measured. Enhancement of neutrophil motility to a chemotactic stimulus of endotoxin-activated autologous serum was observed in normal adult volunteers after the ingestion of 2 and 3 g ascorbate daily. No alteration was observed at lower doses. Other neutrophil functions evaluated that remained unaltered by ascorbate, were postphagocytic hexose monophosphate shunt activity and myeloperoxidase mediated iodination of ingested protein. Stimulation of lymphocyte transformation to the mitogens phytohaemagglutinin and concanavalin A was detected after the daily ingestion of 1, 2, and 3 g of ascorbate. Mitogen-induced protein synthesis was unaffected. Serum levels of IgG, IgA, IgM, C'3, and C'4 and total complement activity were unaltered by ascorbate.

[13] Bendich A. "Vitamin E and immune functions." Basic Life Sci. 1988;49:615-20. Research reported by Clinical Nutrition, Hoffmann La Roche Inc., Nutley, NJ 07110.. =2525= = Author's abstract: Vitamin E, the major lipid-soluble antioxidant present in all cellular membranes, is an important nutrient for optimal immune function. When animals are fed nutritionally complete diets lacking vitamin E, immune responses are adversely affected. Supplementation of these diets with higher than nutritionally adequate levels of vitamin E enhances immune responses. High levels of PUFA are immunosuppressive, and vitamin E can partially overcome this immunosuppression. High levels of vitamin C can protect tissue levels of vitamin E and may indirectly contribute to the immunoenhancement by vitamin E. Severe selenium deficiency is immunosuppressive. Vitamin E can protect some aspects of immune responses from the adverse effects of selenium deficiency. These data clearly indicate that nutrients that affect the overall antioxidant status have important effects on immune functions. In addition, antioxidant nutrient interactions can synergize to overcome the adverse effects of polyunsaturated fatty acids on immune functions.

[14] Meydani SN,Meydani M,Blumberg JB,Leka LS,Siber G,Loszewski R,Thompson C,others. "Vitamin E supplementation and in vivo immune response in healthy elderly subjects. A randomized controlled trial [see comments]" Journal of the American Medical Association. 1997 May 7;277:1380-6. (Issue number 17) (Copy available). Comment in JAMA 1997 May 7;277(17):1398-9 JAMA 1998 Feb 18;279(7):505; discussion 505-6 Research reported by Nutritional Immunology Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111, USA. SvMeydanivIM@HNRC.TUFTS.EDU. =14585= = Conclusion: Our results indicate that a level of vitamin E greater than currently recommended enhances certain clinically relevant in vivo indexes of T-cell-mediated function in healthy elderly persons. No adverse effects were observed with vitamin E supplementation. = Author's abstract: OBJECTIVE: To determine whether long-term supplementation with vitamin E enhances in vivo, clinically relevant measures of cell-mediated immunity in healthy elderly subjects. DESIGN: Randomized, double-blind, placebo-controlled intervention study. SETTING AND PARTICIPANTS: A total of 88 free-living, healthy subjects at least 65 years of age. INTERVENTION: Subjects were randomly assigned to a placebo group or to groups consuming 60, 200, or 800 mg/d of vitamin E for 235 days. MAIN OUTCOME MEASURES: Delayed-type hypersensitivity skin response (DTH); antibody response to hepatitis B, tetanus and diphtheria, and pneumococcal vaccines; and autoantibodies to DNA and thyroglobulin were assessed before and after supplementation. RESULTS: Supplementation with vitamin E for 4 months improved certain clinically relevant indexes of cell-mediated immunity in healthy elderly. Subjects consuming 200 mg/d of vitamin E had a 65% increase in DTH and a 6-fold increase in antibody titer to hepatitis B compared with placebo (17% and 3-fold, respectively), 60-mg/d (41% and 3-fold, respectively), and 800-mg/d (49% and 2.5-fold, respectively) groups. The 200-mg/d group also had a significant increase in antibody titer to tetanus vaccine. Subjects in the upper tertile of serum alpha-tocopherol (vitamin E) concentration (>48.4 micromol/L [2.08 mg/dL]) after supplementation had higher antibody response to hepatitis B and DTH. Vitamin E supplementation had no effect on antibody titer to diphtheria and did not affect immunoglobulin levels or levels of T and B cells. No significant effect of vitamin E supplementation on autoantibody levels was observed.

Meydani SN,Barklund MP,Liu S,Meydani M,and others. "Vitamin E supplementation enhances cell-mediated immunity in healthy elderly subjects." American Journal of Clinical Nutrition. 1990 Sep;52:557-63. (Issue number 3) Comment in Am J Clin Nutr 1991 Apr;53(4):976-7 Copy in office. 97121206 =2246= = Author's abstract: The effect of vitamin E supplementation on the immune response of healthy older adults was studied in a double-blind, placebo-controlled trial. Subjects (n = 32) resided in a metabolic research unit and received placebo or vitamin E (800 mg dl-alpha-tocopheryl acetate) for 30 d. Alpha-tocopherol content of plasma and peripheral blood mononuclear cells (PBMCs), delayed-type hypersensitivity skin test (DTH), mitogen-stimulated lymphocyte proliferation, as well as interleukin (IL)-1, IL-2, prostaglandin (PG) E2, and serum lipid peroxides were evaluated before and after treatment. In the vitamin E-supplemented group 1) alpha-tocopherol content was significantly higher (p less than 0.0001) in plasma and PBMCs, 2) cumulative diameter and number of positive antigen responses in DTH response were elevated (p less than 0.05), 3) IL-2 production and mitogenic response to optimal doses of concanavalin A were increased (p less than 0.05), and 4) PGE2 synthesis by PBMCs (p less than 0.005) and plasma lipid peroxides (p less than 0.001) were reduced. Short-term vitamin E supplementation improves immune responsiveness in healthy elderly individuals; this effect appears to be mediated by a decrease in PGE2 and/or other lipid-peroxidation products

[15] Bendich A. "Vitamin E and immune functions." Basic Life Sci. 1988;49:615-20. Research reported by Clinical Nutrition, Hoffmann La Roche Inc., Nutley, NJ 07110.. =2525= = Author's abstract: Vitamin E, the major lipid-soluble antioxidant present in all cellular membranes, is an important nutrient for optimal immune function. When animals are fed nutritionally complete diets lacking vitamin E, immune responses are adversely affected. Supplementation of these diets with higher than nutritionally adequate levels of vitamin E enhances immune responses. High levels of PUFA are immunosuppressive, and vitamin E can partially overcome this immunosuppression. High levels of vitamin C can protect tissue levels of vitamin E and may indirectly contribute to the immunoenhancement by vitamin E. Severe selenium deficiency is immunosuppressive. Vitamin E can protect some aspects of immune responses from the adverse effects of selenium deficiency. These data clearly indicate that nutrients that affect the overall antioxidant status have important effects on immune functions. In addition, antioxidant nutrient interactions can synergize to overcome the adverse effects of polyunsaturated fatty acids on immune functions.

[16] Meydani SN,Ribaya-Mercado JD,Russell RM,Sahyoun N,and others. "Vitamin B-6 deficiency impairs interleukin 2 production and lymphocyte proliferation in elderly adults." American Journal of Clinical Nutrition. 1991 May;53:1275-80. (Issue number 5) =2086= = Author's abstract: The effect of vitamin B-6 deficiency on immune response was studied in eight healthy elderly adults. The protocol consisted of a 5-d baseline (BL) period; a vitamin B-6-depletion period of less than or equal to 20 d; three stages of vitamin B-6-repletion, each lasting 21 d; and a 4-d final phase. The amounts of vitamin B-6 ingested during the different phases of the study were 3.00, 15.00, 22.50, and 33.75 micrograms.kg body wt-1.d-1, respectively. During the final phase the subjects ingested 50 mg vitamin B-6/d. Fasting blood was collected at the end of each period. Vitamin B-6 depletion significantly decreased percentage and total number of lymphocytes, mitogenic responses of peripheral blood lymphocytes to T- and B-cell mitogens, and interleukin 2 production. These indices returned to BL values after the third vitamin B-6-repletion period, when the total vitamin B-6 intakes were 1.90 +/- 0.18 mg/d for women and 2.88 +/- 0.17 mg/d for men. Vitamin B-6 deficiency impairs in vitro indices of cell-mediated immunity in healthy elderly adults. This impairment is reversible by vitamin B-6 repletion.

[17] Chandra RK. "Grace A. Goldsmith Award lecture. Trace element regulation of immunity and infection." Journal of the American College of Nutrition. 1985;4:5-16. (Issue number 1) =11001= = Author's abstract: Protein-calorie malnutrition is associated with impaired immunocompetence and increased susceptibility to infection. Clinically evident nutritional deficiency syndromes, however, are composite of deficits of many essential nutrients, each of which may exert an important regulating effect on immunity. Among other nutrients, several trace elements have been shown to regulate immune responses, particularly cell-mediated immunity. Zinc undernutrition results in lymphoid atrophy and reduced capacity to respond to many T-cell-dependent antigens. Plaque forming cell response to heterologous erythrocytes is decreased, as is the function of B cells. In zinc deficient rodents, the generation of cytotoxic lymphocytes in the spleen is reduced. Antibody-dependent cell-mediated cytotoxicity is largely unchanged. In acrodermatitis enteropathica, lymphocyte proliferation response to mitogens is decreased and there are significant changes in delayed hypersensitivity responses and in the proportion of various T cell subsets. Neutrophil function is not changed by zinc deficiency. Iron deficiency results in a slight decrease in the number of rosette-forming T cells and a significant impairment of lymphocyte response to mitogens and antigens. Polymorphonuclear leukocytes are unable to kill ingested bacteria and fungi in an efficient manner. Copper deficiency impairs cell-mediated immunity, as does selenium deficiency when it is associated with vitamin E lack. Several pathogenetic mechanisms may underlie such alterations in immunity. Many heavy metals impair immune responses. These effects of trace elements on immunity may have important fundamental and practical implications.

[18] Kiremidjian-Schumacher L,Stotzky G. "Selenium and immune responses." Environ Res. 1987 Apr;42:277-303. (Issue number 2) =11002= = Author's abstract: Selenium (Se) affects all components of the immune system, i.e., the development and expression of nonspecific, humoral, and cell-mediated responses. In general, a deficiency in Se appears to result in immunosuppression, whereas supplementation with low doses of Se appears to result in augmentation and/or restoration of immunologic functions. A deficiency of Se has been shown to inhibit resistance to microbial and viral infections, neutrophil function, antibody production, proliferation of T and B lymphocytes in response to mitogens, and cytodestruction by T lymphocytes and NK cells. Supplementation with Se has been shown to stimulate the function of neutrophils, production of antibodies, proliferation of T and B lymphocytes in response to mitogens, production of lymphokines, NK cell-mediated cytodestruction, delayed-type hypersensitivity reactions and allograft rejection, and the ability of a host to reject transplanted malignant tumors. The mechanism(s) whereby Se affects the immune system is speculative. The effects of Se on the function of glutathione peroxidase and on the cellular levels of reduced glutathione and H2Se, as well as the ability of Se to interact with cell membranes, probably represent only a few of many regulatory mechanisms. The manipulation of cellular levels of Se may be significant for the maintenance of general health and for the control of immunodeficiency disorders and the chemoprevention of cancer.

[19] Peretz A,Neve J,Desmedt J,Duchateau J,and others. "Lymphocyte response is enhanced by supplementation of elderly subjects with selenium-enriched yeast." American Journal of Clinical Nutrition. 1991 May;53:1323-8. (Issue number 5) =4480= = Author's abstract: The effect of selenium supplementation on plasma selenium concentrations and lymphocyte-proliferation responses to mitogens was investigated in 22 elderly institutionalized subjects. Subjects were assigned to a 6-mo trial with either 100 micrograms Se/d (as selenium-enriched yeast) or a placebo. Plasma selenium concentrations of the selenium-supplemented group increased from 0.84 +/- 0.26 to 1.55 +/- 0.33 mumol/L (mean +/- SD) after 2 mo and the values plateaued thereafter. The mean response of lymphocytes to mitogens in elderly subjects tended to be lower than responses in healthy adults, although responses remained within the 5-95% confidence-interval limit for healthy adults. During selenium supplementation the proliferative response to pokeweed mitogen increased significantly (+79% of baseline concentrations after 4 mo, P less than 0.01) and reached the upper limit of the usual range for adults after 6 mo (+138%, P less than 0.001). In accordance with previous studies in animals and in vitro, this investigation demonstrates for the first time immunostimulatory properties of selenium-enriched yeast in elderly humans

[20] Fraker PJ,Jardieu P,Cook J. "Zinc deficiency and immune function." Archives of Dermatology. 1987 Dec;123:1699-701. (Issue number 12) =9546= = Author's abstract: Deficiency in zinc, an essential trace element, is a frequent human dietary problem in the United States and is also associated with such disease states as alcoholism, renal disease, burns, gastrointestinal tract disorders, and acrodermatitis enteropathica. Skin lesions and poor wound healing are observed in severe forms of the deficiency. However, modest deficits in zinc cause lymphopenia and reduced immune capacity among affected humans. With the mouse used as a model because it has an immune system analogues to that of humans, the effects of zinc deficiency on immune function have been well characterized. A suboptimal intake of zinc causes marked atrophy of the thymus, a 50% reduction in leukocytes, a rise in corticosterone levels, and a 40% to 70% reduction in antibody-mediated, cell-mediated, and delayed-type hypersensitivity responses

[21] Chandra RK,Au B. "Single nutrient deficiency and cell-mediated immune responses. I. Zinc." American Journal of Clinical Nutrition. 1980 Apr;33:736-8. (Issue number 4) =9278= = Author's abstract: The thymus of rats provided zinc-deficient diet weighed less than the thymus of animals fed zinc-containing control diet. The antibody-forming cell response in the spleen was reduced. Cytotoxic response of spleen cells of zinc-deficient mice immunized in vivo was decreased whereas after sensitization in vitro the response was comparable to that seen in zinc-replete animals. Natural killer cell activity and antibody-dependent cell-mediated cytotoxicity were increased, particularly the former. These observations suggest that dietary zinc intake is an important factor modulating cell-mediated immune responses.

[22] Prasad AS. "Zinc: an overview." Nutrition. 1995 Jan-Feb;11:93-9. (Issue number 1 Suppl) =9324= = Author's abstract: Zn deficiency in humans is widespread throughout the world. It is more prevalent in areas where the population subsists on cereal proteins. Conditioned Zn deficiency is seen in many disease states. Its deficiency during growth periods results in growth failure and lack of gonadal development in males. Other effects of Zn deficiency include skin changes, poor appetite, mental lethargy, delayed wound healing, neurosensory disorders, and cell-mediated immune disorders. Severe Zn deficiency, as seen in acrodermatitis enteropathica (a genetic disorder), is fatal if Zn is not administered to these patients. A clinical diagnosis of marginal Zn deficiency in humans remains problematic. Assays of Zn in granulocytes and lymphocytes provide better diagnostic criteria for marginal Zn deficiency than plasma Zn. Approximately 300 enzymes are known to require Zn for their activities. Zn is required for DNA synthesis, cell division, and protein synthesis. Recently, we learned that Zn-finger proteins are involved in genetic expression of various growth factors and steroid receptors. We suspect that several hundred Zn-containing nucleoproteins are probably involved in gene expression of various proteins. Zn deficiency adversely affects lymphocyte proliferation. This may be related to the enzymatic role of Zn in DNA synthesis and cell division. Thymulin, a thymic hormone involved in T-lymphocyte maturation, is known to be Zn dependent and is adversely affected by Zn deficiency. Thus, an adverse effect of Zn deficiency may also be in lymphocyte differentiation and maturity. Zn deficiency is known to decrease interleukin 2 production by helper T lymphocytes, and abnormalities in T-lymphocyte subpopulations have been observed in Zn-deficient humans.(ABSTRACT TRUNCATED AT 250 WORDS)

[23] Mulhern SA,Koller LD. "Severe or marginal copper deficiency results in a graded reduction in immune status in mice." J Nutr. 1988 Aug;118:1041-7. (Issue number 8) =9551= = Author's abstract: From birth mice received diets containing copper at 0.5, 1, 2 or 6 mg/kg diet. At 8 wk of age they were killed and copper status and immune responsiveness were determined. Only the groups that received copper at 0.5 or 1 mg/kg showed signs of copper deficiency, such as reduced serum ceruloplasmin, hemoglobin, hematocrit and red blood cell counts and characteristic changes in organ pathology. Body and lymphoid organ weights were altered in the groups that received copper at 0.5 or 1 mg/kg. Males were more severely affected than females. A dose-related reduction in splenic T-cell subpopulations was noted in the 0.5 and 1 mg/kg groups. Responses to lipopolysaccharide challenge were reduced, and an increase in spontaneous cycling cells was noted in the groups receiving copper at 0.5 or 1 mg/kg. Only the group receiving copper at 0.5 mg/kg had increased stem cell activity; this increase was probably due to increased erythropoiesis to meet increased demands for red blood cells in this group. These data indicate that only groups receiving copper at 0.5 or 1 mg/kg in the diet were depleted and marginally depleted in copper, respectively, and that immune hyporesponsiveness differs between the depleted and marginally depleted groups.

[24] Galland L. "Magnesium and immune function: an overview." Magnesium. 1988;7:290-9. (Issue number 5-6) =2715= = Author's abstract: Mg participates in immune responses in numerous ways: as a cofactor for immunoglobulin synthesis, C'3 convertase, immune cell adherence, antibody-dependent cytolysis, IgM lymphocyte binding, macrophage response to lymphokines, T helper-B cell adherence, binding of substance P to lymphoblasts and antigen binding to macrophage RNA. Mg deficiency in rodents impairs IgG synthesis and cell-mediated immunity; complications include thymus atrophy, elevated IgE, hypereosinophilia, histaminosis and lymphoma. Immunologic sequelae of Mg deficiency in humans are subtle and may be affected by genetic control of blood cell Mg concentration. Abnormal C' activation, excess antibody production and susceptibility to allergy and to chronic fungal and viral infections have been reported. Mg appears to play a protective role in acute allergic reactions.

[25] *"Effect of vitamin and trace mineral supplementation on immune responses and infection in elderly subjects" Lancet. 1992 Nov 7;340:1124. Copy in office. 93030601 =4896= In this randomized controlled trial and elderly, 96 independently living elderly subjects were given physiologic amounts of multiple vitamins and trace elements or placebo. The treated group were ill from infection 23 days per year compared to 48 days in the control group. Cells and substances associated with immunocompetence were also increased in the study group. The supplement contained vit A 400 retinol equivalents, beta-carotene 16 milligrams, thiamine 2.2 milligrams, riboflavin 1.5 milligrams, niacin 16 milligrams, pyridoxine 3 milligrams, folate 400 micrograms, vitamin B12 4 micrograms, vitamin C 80 milligrams, vitamin D 4 micrograms, vitamin E 44 milligrams, iron 16 milligrams, zinc 14 milligrams, copper 1.4 milligrams, selenium 20 micrograms, iodine 0.2 milligrams, calcium 200 milligrams, and magnesium 100 milligrams. The placebo contained calcium and magnesium.

Chandra RK. "Effect of vitamin and trace-element supplementation on immune responses and infection in elderly subjects [see comments]" Lancet. 1992 Nov 7;340:1124-7. (Issue number 8828) Comment in Lancet 1993 Jan 30;341(8840):306-7 according to NAH 1994 Aug page 10. Research reported by Memorial University of Newfoundland.. =7993= = Author's abstract: Ageing is associated with impaired immune responses and increasedinfection-related morbidity. This study assessed the effect of physiological amounts of vitamins and trace elements on immunocompetence and occurrence of infection-related illness. 96 independently living, healthy elderly individuals were randomly assigned to receive nutrient supplementation or placebo. Nutrient status and immunological variables were assessed at baseline and at 12 months, and the frequency of illness due to infection was ascertained. Subjects in the supplement group had higher numbers of certain T-cell subsets and natural killer cells, enhanced proliferation response to mitogen, increased interleukin-2 production, and higher antibody response and natural killer cell activity. These subjects were less likely than those in the placebo group to have illness due to infections (mean [SD] 23 [5] vs 48 [7] days per year, p = 0.002). Supplementation with a modest physiological amount of micronutrients improves immunity and decreases the risk of infection in old age.

[26] Girodon F,Lombard M,Galan P,Brunet-Lecomte P,Monget AL,Arnaud J,Preziosi P,others. "Effect of micronutrient supplementation on infection in institutionalized elderly subjects: a controlled trial." Annals of Nutrition and Metabolism. 1997;41:98-107. (Issue number 2) =11432= = Author's abstract: To determine the impact of a trace element and vitamin supplementation on infectious morbidity, a double-blind controlled trial was performed on 81 elderly subjects in a geriatric center during a 2-year period. Subjects were randomly assigned to one of four treatment groups, and received daily: placebo; trace elements/zinc 20 mg; selenium 100 micrograms); vitamins (vitamin C 120 mg; beta-carotene 6 mg; alpha-tocopherol 15 mg); or a combination of trace elements and vitamins at equal doses. (1) Before supplementation, low serum values in vitamin C, folate, zinc and selenium were observed in more than two thirds of the patients. (2) After 6 months of supplementation, a significant increase in vitamin and trace element serum levels was obtained in the corresponding treatment groups: a plateau was then observed for the whole study. (3) Subjects who received trace elements (zinc and selenium) alone or associated with vitamins had significantly less infectious events during the 2 years of supplementation. These results indicate that supplementation with low doses of vitamins and trace elements is able to rapidly correct corresponding deficiencies in the institutionalized elderly. Moreover, zinc and selenium reduced infectious events.

[27] Chandra RK. "Effect of vitamin and trace-element supplementation on immune responses and infection in elderly subjects [see comments]" Lancet. 1992 Nov 7;340:1124-7. (Issue number 8828) Comment in Lancet 1993 Jan 30;341(8840):306-7 according to NAH 1994 Aug page 10. Research reported by Memorial University of Newfoundland.. =7993= = Author's abstract: Ageing is associated with impaired immune responses and increased infection-related morbidity. This study assessed the effect of physiological amounts of vitamins and trace elements on immunocompetence and occurrence of infection-related illness. 96 independently living, healthy elderly individuals were randomly assigned to receive nutrient supplementation or placebo. Nutrient status and immunological variables were assessed at baseline and at 12 months, and the frequency of illness due to infection was ascertained. Subjects in the supplement group had higher numbers of certain T-cell subsets and natural killer cells, enhanced proliferation response to mitogen, increased interleukin-2 production, and higher antibody response and natural killer cell activity. These subjects were less likely than those in the placebo group to have illness due to infections (mean [SD] 23 [5] vs 48 [7] days per year, p = 0.002). Supplementation with a modest physiological amount of micronutrients improves immunity and decreases the risk of infection in old age.

Bogden JD,Bendich A,Kemp FW,Bruening KS,Shurnick JH,Denny T,others. "Daily micronutrient supplements enhance delayed-hypersensitivity skin test responses in older people." American Journal of Clinical Nutrition. 1994 Sep;60:437-47. (Issue number 3) Research reported by Department of Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School, Newark 07103-2714.. =5763= Supplement improves immune function in the elderly: This study suggests that many apparently healthy elderly individuals have marginal deficiencies of one or more micronutrients and that these deficiencies adversely affect cell-mediated immunity. A previous study has shown that among elderly individuals who take a supplement, the incidence of infections is reduced by nearly 50%. Theragran M contains only small quantities of vitamins B, C and E; calcium, magnesium, chromium, and selenium. Although this low-potency formula improves immune function in the healthy elderly, it islikely that people with acute or chronic illnesses would need a higher-dose formula. = Author's abstract: A placebo-controlled double-blind trial of the effects of daily micronutrient supplements on circulating vitamin and trace metal concentrations and delayed-hypersensitivity skin test (DHST) responses was conducted. Subjects, aged 59-85 y, were randomly assigned to placebo (n = 27) or micronutrient (n = 29) treatment groups. DHST and circulating concentrations of nine micronutrients were measured before and after 6 and 12 mo of micronutrient ingestion. For the micronutrient group, there were statistically significant increases at 6 and/or 12 mo in the mean serum concentrations of ascorbate, beta-carotene, folate, vitamin B-6, and alpha-tocopherol. There was a significant increase at 12 mo in the number of subjects in the placebo group with one or more low concentrations. DHST responses to a panel of seven recall antigens were significantly increased at 12 mo in the micronutrient group but not the placebo group. This study demonstrates that daily supplementation with low-to-moderate doses of micronutrients can prevent low concentrations of some micronutrients and can improve DHST responses in healthy, independently living older adults.

[28] Horrobin DF,Manku MS,Oka M,Morgan RO,Cunnane SC,Ally AI,Ghayur T,others. "The nutritional regulation of T lymphocyte function." Medical Hypotheses. 1979 Sep;5:969-85. (Issue number 9) =5170= = Author's abstract: Prostaglandin (PG) E1 plays a major role in the regulation of thymus development and T lymphocyte function and the evidence for this is reviewed. The production of PGE1 is dependent on nutritional factors with linoleic acid, gamma-linolenic acid, pyridoxine, zinc and vitamin C playing key roles. Inadequate intake of any oneof these will lead to inadequate PGE1 formation and defective T lymphocyte function. Megadoses of any one are likely to be only minimally effective in the absence of adequate intakes of the others. By careful attention to diet it should be possible to activate T lymphocyte function in the large number of diseases including rheumatoid arthritis, various auto-immune diseases, multiple sclerosis, and cancer in which such function is defective. It is possible that T lymphocytes may require both endogenous and exogenous PGE1 in order to function adequately. It is therefore of particular interest that many cancer cells and virally infected cells are unable to make PGE1 because they cannot convert linoleic acid to gamma-linolenic acid. The direct provision of gamma-linolenic or dihomo-gammalinolenic acids in these situations is worthy of full investigation.

[29] Folkers K,Morita M,McRee J Jr. "The activities of coenzyme Q10 and vitamin B6 for immune responses." Biochem Biophys Res Commun. 1993 May 28;193:88-92. (Issue number 1) Research reported by Institute for Biomedical Research, University of Texas, Austin 78712.. =5189= = Author's abstract: Coenzyme Q10 (CoQ10) and vitamin B6 (pyridoxine) have been administered together and separately to three groups of human subjects. The blood levels of CoQ10 increased (p < 0.001) when CoQ10 and pyridoxine were administered together and when CoQ10 was given alone. The blood levels of IgG increased when CoQ10 and pyridoxine were administered together (p < 0.01) and when CoQ10 was administered alone (p < 0.05). The blood levels of T4-lymphocytes increased when CoQ10 and pyridoxine were administered together (p < 0.01) and separately (p < 0.001). The ratio of T4/T8 lymphocytes increased when CoQ10 and pyridoxine were administered together (p < 0.001) and separately (p < 0.05). These increases in IgG and T4-lymphocytes with CoQ10 and vitamin B6 are clinically important for trials on AIDS, other infectious diseases, and on cancer.

[30] Daly JM,Reynolds J,Sigal RK,Shou J,Liberman MD. "Effect of dietary protein and amino acids on immune function." Critical Care Medicine. 1990 Feb;18:S86-93. (Issue number 2 Suppl) =9526= = Author's abstract: The normal immune system has local and systemic components which are influenced by a variety of alterations. Impaired host immunity is associated with neoplasia, protein calorie malnutrition, and the administration of immunosuppressive drugs. It is well accepted that protein calorie malnutrition impairs host immunity with particular detrimental effects on the T-cell system, resulting in increased opportunistic infection and increased morbidity and mortality in hospitalized patients. Individual nutrient substrates may also have a major influence on the immune system. Individual amino acids are often described as essential, based on requirements for optimal growth and maintenance of positive N balance. Arginine has been demonstrated to be essential to the traumatized host and may have tissue-specific properties which influence components of the immune system. Thus, arginine may be of value in clinical situations where the immune system is compromised. In a series of experiments in normal animals, arginine was demonstrated to enhance cellular immune mechanisms, in particular T-cell function. It also has a marked immunopreserving effect in the face of immunosuppression induced by protein malnutrition and increases in tumor burden. In postoperative surgical patients, arginine supplementation results in enhanced T-lymphocyte response and augmented T-helper cell numbers, with a rapid return to normal of T-cell function postoperatively compared with control patients. These data suggest that arginine supplementation may enhance or preserve immune function in high-risk surgical patients and theoretically improve the host's capacity to resist infection.

[31] Azzara A,et al,Carulli G,Sbrana S,Rizzuti-Gullaci A,Minnucci S,Natale M,Ambrogi F. "Effects of lysine-arginine association on immune functions in patients with recurrent infections." Drugs Exp Clin Res. 1995;21:71-8. (Issue number 2) Lysine/arginine enhances immune function: Lysine and arginine have both been reported to have beneficial effects on the immune system. When given in combination, these amino acids reversed the age-related decline in thymic activity in both mice and elderly humans. Lysine/arginine was also effective in children with recurrent respiratory infections. The combination has been found to enhance neutrophil function in vitro, although neither amino acid alone had an effect. A gram or two each per day of lysine and arginine may therefore be considered for adults with recurrent infections (remember that the 4 g/day doses mentioned above included the weight of pyrrolidon-carboxylate). It should be noted, however, that supplementation with arginine can provoke a recurrence of herpes simplex, which requires arginine for replication. = Author's abstract: Combined L-lysine-L-arginine therapy is capable of inducting recovery in age-related decline of thymic activity in mice and in elderly humans. The clinical usefulness of the association has also been shown in children with recurrent respiratory infections, while an increase in the number of CD3+ lymphocytes has been shown in patients with chronic lymphatic leukaemia. Recently, in vitro effects of the association on neutrophil function have been reported. In particular, the association was able to increase random migration, chemotaxis, phagocytosis-associated- and f-MLP-induced chemiluminescence. In this paper the authors evaluate the effects of L-lysine-L-arginine combination (lisargin) on several humoral and cell-mediated immunologic parameters in patients with recurrent infection. An increase of neutrophil random migration and chemotaxis (evaluated by a new technique, based on a computer assisted image processing system) was found. Furthermore an increase in the absolute number of lymphocytes involved in cytotoxic activity and IgG levels was observed.

[32] De Flora S,Grassi C,Carati L. "Attenuation of influenza-like symptomatology and improvement of cell-mediated immunity with long-term N-acetylcysteine treatment." European Respiratory Journal. 1997 Jul;10:1535-41. (Issue number 7) Research reported by Institute of Hygiene and Preventive Medicine, University of Genoa, Italy.. =15128= = Author's abstract: N-acetylcysteine (NAC), an analogue and precursor of reduced glutathione, has been in clinical use for more than 30 yrs as a mucolytic drug. It has also been proposed for and/or used in the therapy and/or prevention of several respiratory diseases and of diseases involving an oxidative stress, in general. The objective of the present study was to evaluate the effect of long-term treatment with NAC on influenza and influenza-like episodes. A total of 262 subjects of both sexes (78% > or = 65 yrs, and 62% suffering from nonrespiratory chronic degenerative diseases) were enrolled in a randomized, double-blind trial involving 20 Italian Centres. They were randomized to receive either placebo or NAC tablets (600 mg) twice daily for 6 months. Patients suffering from chronic respiratory diseases were not eligible, to avoid possible confounding by an effect of NAC on respiratory symptoms. NAC treatment was well tolerated and resulted in a significant decrease in the frequency of influenza-like episodes, severity, and length of time confined to bed. Both local and systemic symptoms were sharply and significantly reduced in the NAC group. Frequency of seroconversion towards A/H1N1 Singapore 6/86 influenza virus was similar in the two groups, but only 25% of virus-infected subjects under NAC treatment developed a symptomatic form, versus 79% in the placebo group. Evaluation of cell-mediated immunity showed a progressive, significant shift from anergy to normoergy following NAC treatment. Administration of N-acetylcysteine during the winter, thus, appears to provide a significant attenuation of influenza and influenza-like episodes, especially in elderly high-risk individuals. N-acetylcysteine did not prevent A/H1N1 virus influenza infection but significantly reduced the incidence of clinically apparent disease.

[33] Kelly GS. "Larch arabinogalactan: clinical relevance of a novel immune-enhancing polysaccharide." Alternative Medicine Review. 1999 Apr;4:96-103. (Issue number 2) =13256= = Author's abstract: Larch arabinogalactan is composed of greater than 98-percent arabinogalactan, a highly branched polysaccharide consisting of a galactan backbone with side-chains of galactose and arabinose sugars. Larch arabinogalactan is an excellent source of dietary fiber, and has been approved as such by the FDA. It has been shown to increase the production of short-chain fatty acids, principally butyrate and propionate, and has been shown to decrease the generation and absorption of ammonia. Evidence also indicates human consumption of larch arabinogalactan has a significant effect on enhancing beneficial gut microflora, specifically increasing anaerobes such as Bifidobacteria and Lactobacillus. Larch arabinogalactan has several interesting properties which appear to make it an ideal adjunctive supplement to consider in cancer protocols. Experimental studies have indicated larch arabinogalactan can stimulate natural killer (NK) cell cytotoxicity, enhance other functional aspects of the immune system, and inhibit the metastasis of tumor cells to the liver. The immune- enhancing properties also suggest an array of clinical uses, both in preventive medicine, due to its ability to build a more responsive immune system, and in clinical medicine, as a therapeutic agent in conditions associated with lowered immune function, decreased NK activity, or chronic viral infection.

[34] Bone K. "Astragalus" Nutrition and Healing. 2001 Jul;8:5. (Issue number 7) (Copy available). =16656= Astragalus membranaceus relieves leukopenia (especially in combination with Withania somnifera), and so helpful following chemotherapy and radiation therapy. It has been shown to increase body weight after chemotherapy in comparison to placebo. It has been shown to relieve angina and improve vision, strength and cellular immunity in the aged. Dose should be at least 2 grams daily of the root. Best to avoid it during the acute stages of infection, Bone believes.

[35] Sharma ML,Khajuria A,Kaul A,others. "Effect of salai guggal ex-Boswellia serrata on cellular and humoral immune responses and leucocyte migration." Agents Actions. 1988 Jun;24:161-4. (Issue number 1-2) Research reported by Pharmacology Department, Regional Research Laboratory, Jammu Tawi, India.. =1146= = Author's abstract: Effect of alcoholic extract of salai guggal (AESG) was studied on cellular and humoral immune responses in mice and leucocyte migration in rats. Oral administration of AESG strongly inhibited the antibody production and cellular responses to sheep red blood cells in mice. It inhibited the infiltration of polymorphonuclear leucocytes and reduced the volume of pleural exudate in carrageenan induced pleurisy in rats. It showed no cytotoxic effect.

[36] Kalmar L,Kadar J,Somogyi A,Gergely P,Csomos G,Feher J. "Silibinin (Legalon-70) enhances the motility of human neutrophils immobilized by formyl-tripeptide, calcium ionophore, lymphokine and by normal human serum." Agents Actions. 1990 Mar;29:239-46. (Issue number 3-4) according to TLfD 1994 page 130:438. Research reported by Second Department of Medicine, Semmelweis University, Budapest, Hungary.. =4496= = Author's abstract: Experiments reported here were designed to investigate the effect of silibinin (extracted from Silybum marianum) on human polymorphonuclear leukocyte (PMN) motility and on leukocyte immobilizing activity of lymphokine (leukocyte inhibitory factor, LIF), formyl-Met-Leu-Phe (fMLP), calcium ionophore A-23187 and human sera inactivated by heat (HI-S). In the in vitro experiments, silibinin (1-10 micrograms/ml) failed to influence the random motility of unstimulated PMNS in agarose droplet assay, but enhanced the motility of the PMNs immobilized by fMLP, calcium ionophore, LIF or by autologous human sera. In the in vivo study, silibinin (Legalon-70) two hours after the administration was effective in enhancing spontaneous motility of leukocytes obtained from health volunteers which action could be regarded as a consequence of the decrease of leukocyte immobilizing activity being present in normal human plasma.

[37] Atal CK,Sharma ML,Kaul A,Khajuria A. "Immunomodulating agents of plant origin. I: Preliminary screening." J Ethnopharmacol. 1986 Nov;18:133-41. (Issue number 2) =10503= = Author's abstract: The immunobiological activity was investigated of certain medicinal plants widely used in the Ayurvedic and Unani systems of medicine for treatment of chronic infections and immunological disorders. The effect of an ethanolic extract of each drug was studied on delayed type hypersensitivity, humoral responses to sheep red blood cells, skin allograft rejection, and phagocytic activity of the reticuloendothelial system in mice. Picrorhiza kurroa was found to be a potent immunostimulant, stimulating both cell-mediated and humoral immunity. Tylophora indica, Aconitum heterophyllum and Holarrhena antidysenterica appeared to stimulate phagocytic function while inhibiting the humoral component of the immune system. Tinospora cordifolia and Ocimum gratissimum appeared to improve the phagocytic function without affecting the humoral or cell-mediated immune system. Hemidesmus indicus suppressed both the cell-mediated and humoral components of the immune system.

[38] *Sanchez A,Reeser JL,Lau HS,Yahiku PY,Willard RE,McMillan PJ,others. "Role of sugars in human neutrophilic phagocytosis." American Journal of Clinical Nutrition. 1973 Nov;26:1180-4. (Issue number 11) according to NH 1994 Nov page 11. =6994= Simple sugars, but not complex carbohydrates, impair bacterial phagocytosis (Quillen summary: he quotes other sources in support of the idea that tumors selectively metabolise glucose, and that epidemiologic evidence indicates that high sugar intake is a major risk factor for cancer).

[39] Ringsdorf WM Jr,Cheraskin E,Ramsay RR Jr. "Sucrose, neutrophilic phagocytosis and resistance to disease." Dent Surv. 1976 Dec;52:46-8. (Issue number 12) according to NAH 1994 Nov page 1. =8017= Healthy young adults drank 66 grams of sucrose in 24 ounces of cola. Leukocyte phagocytic ability fell by 50% in 45 minutes.

[40] Tietz NW,Thompson J. "Possible concentration-dependent suppression of immune response by verapamil." Archives of Family Medicine. 1995 Apr;4:368-9. (Issue number 4) (Copy available). Research reported by University of Kentucky Medical Center, Lexington, USA.. =6838= = Author's abstract: Calcium channel blockers inhibit in vitro the lymphocyte response to mitogens and the generation of cytotoxic T-cell and natural killer cell activity. We report on a patient taking verapamil hydrochloride who experienced repeated, prolonged viral infections. His lymphocyte response to phytohemagglutinin, pokeweed mitogen, and tetanus antigen were suppressed; the mononuclear response to soluble tetanus was markedly diminished; and there was no response to influenza vaccination. On lowering the verapamil dose, or changing therapy to clonidine hydrochloride, all the above-mentioned functions returned to normal and a response to influenza vaccination was observed. We speculate that the prolonged viral infection observed in this patient may have been caused by suppression of the immune response by verapamil and we encourage further boad-based studies.

[41] Bendich A. "Vitamin E and immune functions." Basic Life Sci. 1988;49:615-20. Research reported by Clinical Nutrition, Hoffmann La Roche Inc., Nutley, NJ 07110.. =2525= = Author's abstract: Vitamin E, the major lipid-soluble antioxidant present in all cellular membranes, is an important nutrient for optimal immune function. When animals are fed nutritionally complete diets lacking vitamin E, immune responses are adversely affected. Supplementation of these diets with higher than nutritionally adequate levels of vitamin E enhances immune responses. High levels of PUFA are immunosuppressive, and vitamin E can partially overcome this immunosuppression. High levels of vitamin C can protect tissue levels of vitamin E and may indirectly contribute to the immunoenhancement by vitamin E. Severe selenium deficiency is immunosuppressive. Vitamin E can protect some aspects of immune responses from the adverse effects of selenium deficiency. These data clearly indicate that nutrients that affect the overall antioxidant status have important effects on immune functions. In addition, antioxidant nutrient interactions can synergize to overcome the adverse effects of polyunsaturated fatty acids on immune functions.

[42] Caetano JA,Parames MT,Babo MJ,Santos A,Ferreira AB,Freitas AA,Coelho MR,others. "Immunopharmacological effects of Saccharomyces boulardii in healthy human volunteers." Int J Immunopharmacol. 1986;8:245-59. (Issue number 3) =9431= = Author's abstract: Investigation of oral administration of Saccharomyces boulardii in healthy volunteers demonstrates several cellular and humoral changes in peripheral blood. Among its effects are the increase of erythrocytes, leucocytes, polymorphs, neutrophils, complement components C3, C5, C3d, serum anticomplementary activity and leucocyte chemokinesis, specially when autologous serum and antigen have been added to the culture medium and decrease of complement haemolytic activity (CH50, classic and alternative pathways). We have also demonstrated that in vitro S. boulardii was able to activate complement directly, to fix C3b to its surface and that its phagocytosis by mononuclear cells was complement-dependent. The overall changes in serum proteins suggested changes of acute phase proteins typical of an inflammatory process. Furthermore S. boulardii had no mitogenic response of lymphocyte populations. Our results demonstrated that S. boulardii activates the reticuloendothelial system and complement system and suggest that S. boulardii merits therapeutic trial in a variety of clinical situations.

[43] Hsia J,Sarin N,Oliver JH,Goldstein AL. "Aspirin and thymosin increase interleukin-2 and interferon-gamma production by human peripheral blood lymphocytes." Immunopharmacology. 1989 May-Jun;17:167-73. (Issue number 3) Language- eng Research reported by Department of Medicine, George Washington University School of Medicine and Health Sciences, Washington, DC 20037.. =16685= = Author's abstract: Interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) have recently been added to the arsenal of synthetic biological response modifiers with important immunomodulatory activities. In this paper we have assessed the effects of acetylsalicylic acid (aspirin), thymosin alpha and thymosin fraction 5 (TF5), a partially purified calf thymic preparation, on production of IFN-gamma in vitro. Stimulation by oral aspirin of IL-2 and IFN-gamma production by peripheral blood lymphocytes (PBLs) was also studied in healthy human volunteers. Aspirin, thymosin alpha 1 and TF5 were all observed to enhance phytohemagglutinin (PHA)-stimulated production of IFN-gamma. Peak IFN-gamma production by PHA-stimulated PBLs was observed after 24 h of incubation with TF5 and after 72 h with aspirin. Stimulation by aspirin and TF5 required the presence of macrophages, and was additive and dose-dependent. The additive effects of aspirin and TF5 suggest that these agents act by different mechanisms. Oral administration of aspirin in normal volunteers significantly enhanced production of both IFN-gamma and IL-2. PHA-stimulated IFN-gamma production was greatest 24 h after aspirin ingestion; in contrast, IL-2 production was optimal 10 h after aspirin ingestion. These observations suggest that oral aspirin is an effective biological response modifier in humans and raise the possibility of a novel combination approach to immunomodulation involving cyclooxygenase inhibitors and thymosins

[44] Hockertz S,Heckenberger R. "Treatment of an acute bacterial infection with a combination of acetylsalicylic acid/ibuprofen and interferon gamma." Arzneimittelforschung. 1996 Oct;46:1012-5. (Issue number 10) Language- eng Research reported by Fraunhofer Department of Toxicology and Environmental Medicine, Hamburg.. =16678= = Author's abstract: The bacterial infection with Listeria monocytogenes is associated with an inhibition of the macrophage function, the first-line defense against bacterial infection. We studied the effect of acetylsalicylic acid (ASA, CAS 50-78-2) and ibuprofen (CAS 15687-21-1) alone and in combination with a suboptimal dose of recombinant interferon gamma. (IFN gamma) on the acute infection with Listeria monocytogenes in the Balb/c mouse. Animals were intravenously infected with a sublethal dose of Listeria monocytogenes. The therapy was carried out I) at the time of the infection, II) 30 min, III) 60 min, IV) 3 h and V) 24 h post infection. Six groups of mice were treated: i) untreated control, ii) 10(4) units IFN gamma, iii) 10 mg/kg ASA, i.v.) 10 mg/kg ASA + IFN gamma, i.v.) 12 mg/kg ibuprofen, and vi) 12 mg/kg ibuprofen + IFN gamma. The data shown that treatment with ibuprofen and ASA resulted in a significant reduction of viable bacteria in spleen and liver, the main organs of this infection. In combination with low dose interferon gamma, both non-steroidal anti-inflammatory drugs (NSAID) reduced the parasite burden in the examined organs by a factor of more than 10. The therapeutic efficacy showed its maximum 1 h after challenge with Listeria monocytogenes. These results suggest that ibuprofen and ASA possess antibacterial activity. In addition, IFN gamma significantly increases the antibacterial activity of ASA and ibuprofen. Presumably, these effects are due to an influence on the host immune system.