Vitamin B6, although having no antioxidant properties, plays an important part in antioxidant defences, because of its action in the metabolic pathway for the formation of cysteine, which, as indicated earlier, is the rate-limiting precursor in glutathione synthesis. Vitamin B6 status has widespread effects upon immune function (Rall and Meydani, 1993). Vitamin B6 deficiency causes thymic atrophy and lymphocyte depletion in lymph nodes and spleen. Antigen processing is unaffected. However, the ability to make antibodies to sheep red blood cells is depressed. In human studies, the ability to make antibodies to tetanus and typhoid antigens is not seriously affected. Various aspects of cellmediated immunity are also influenced by vitamin B6 deficiency. Skin grafts in rats and mice survive longer during deficiency, and guinea pigs exhibit decreased delayed-hypersensitivity reactions to bacillus Calmette-Guerin (BCG) administration. Deficiency of vitamin B6 is rare in humans but can be precipitated with the anti-tuberculosis (anti-TB) drug isoniazid. However, experimental deficiency in elderly subjects has been shown to reduce total blood lymphocyte numbers and decrease the proliferative response of lymphocytes to mitogens (Meydani et al., 1991). Likewise, IL-2 production is reduced by deficiency of the vitamin. Restoration of vitamin B6 intake to normal by dietary supplements restores immune function. However, intakes that are higher than current recommended values are required to normalize all immune functions, suggesting that this vitamin can only restore immune function in this way. It is unclear, at present, whether a similar situation occurs in younger subjects.
One mechanism for the effect of vitamin B6 on immune function may be due to the importance of the vitamin in cysteine synthesis, as outlined earlier. Deficiency of the vitamin may limit the availability of cysteine for glutathione synthesis. In rats, vitamin B6 deficiency resulted in decreases of 12 and 21% in glutathione concentrations in plasma and spleen, respectively (Takeuchi et al., 1991). In healthy young women, large doses of vitamin B6 (27 mg day-1 for 2 weeks) resulted in a 50% increase in plasma cysteine content (Kang-Yoon and Kirksey, 1992), presumably by increased flux through the transulphuration pathway. As cysteine is a rate-limiting substrate for glutathione synthesis, these findings may have implications for the response to pathogens, because of the importance of glutathione in lymphocyte proliferation and antioxidant defence. However, while vitamin B6 has cellular effects on the immune system, evidence is lacking of any effect upon the inflammatory response.
High concentrations of vitamin C are found in phagocytic cells. While the role of vitamin C as a key component of antioxidant defence is well established (Fig. 7.6), most studies have shown only minor effects upon a range of immune functions (see Hughes, Chapter 9, this volume), except in cases where the vitamin may be acting by interacting with GSH metabolism. Unlike deficiencies in vitamins B6, and E and riboflavin, deficiency of vitamin C does not cause atrophy of lymphoid tissue. In a study of ultramarathon runners, dietary supplementation with 600 mg day-1 of ascorbic acid reduced the incidence of upper respiratory-tract infections after a race by 50% (Peters et al., 1993). It is interesting to note that strenuous exercise has been shown to deplete tissue glu-tathione content. The interrelationship between glutathione and ascorbic acid may therefore play a role in the effect of exercise on immune function.
When immunological parameters and antioxidant status were measured in adult males fed 250 mg day-1 of vitamin C for 4 days, followed by 5 mg day-1 for 32 days, plasma ascorbic acid and glutathione decreased and impairment of antioxidant status became evident from a doubling in semen 8-hydroxydeoxyguanosine concentration (a measure of oxidative damage to nucleic acids) during the second dietary period (Jacob et al., 1991). A fall in vitamin content in peripheral-blood mononuclear cells was noted and the delayed-type hypersensitivity reaction to seven recall antigens was significantly reduced in intensity.
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