MODULATION OF INTERLEUKIN PRODUCTION BY ASCORBIC-ACID

We studied the influence of ascorbate (vitamin C) on peripheral blood mononuclear cells (PBMC) of pigs with hereditary deficiency in ascorba te synthesis. Groups of animals were depleted of, or supplemented with dietary ascorbate for up to 5 weeks. B lymphocytes and T lymphocyte s ubsets differed in the two experimental groups only marginally and tra nsiently as determined by analysis of cell surface markers. The prolif erative response of PBMC to B and T lymphocyte mitogens was lower in d epleted as compared to supplemented animals. Interleukin (IL)-2 and IL -6 were determined by bioassays and were secreted within few hours aft er mitogenic activation of PBMC which contained normal physiological c oncentrations of ascorbate. IL-2 production peaked at about 24 h of in vitro culture after Con A activation, but it lasted for 2-3 days afte r PWM activation. The production of IL-2 and IL-6 were compared during systemic depletion and supplementation with ascorbate. Depleted PBMC produced IL-2 which accumulated in cultures instead of being rapidly c onsumed by n-2 dependent cell growth. This suggests that cellular asco rbate influences the production of n-2. Secretion of IL-6 by mitogen a ctivated PBMC was also affected by prolonged dietary ascorbate depleti on. The results suggest that ascorbate levels exert an early effect on immune homeostasis via reactive oxygen intermediates (ROI) -dependent expression of interleukin genes, since the transcription factor NF-ka ppa B is sensitive to ROI and regulates the expression of interleukin genes. (C) 1998 Elsevier Science B.V. All rights reserved.