RESISTANCE OF C57B1/6 MICE TO IMMUNOSUPPRESSIVE EFFECTS OF AFLATOXIN-B1 AND RELATIONSHIP WITH NEUROENDOCRINE MECHANISMS

Aflatoxin B1 (AFB1) a secondary metabolite of Aspergillus flavus and A. parasiticus, is known for its carcinogenicity and immunosuppressive effects. We previously reported on the immunosuppressive effects of AFB1 in Swiss and CD-1 mice. This study concerned the involvement of the hypothalamus-pituitary-adrenal gland axis in the immunosuppressive effects of AFB1 in C57Bl/6 mice. Animals were treated orally with 30, 150 or 750-mu-g/kg AFB1 daily for four weeks. Splenic lymphocytes were assayed to investigate their phenotyping using flow cytometry, proliferative response against mitogens and allogeneic lymphocytes, cytolytic cell activity, and IL-2 production. Antibody-mediated immunocompetence was checked using sheep red blood cell (SRBC)-challenged animals by plaque-forming cell assay and enzyme-linked immunosorbent assay. The dose of AFB1 for the immunosuppressive effects on blastogenic response, IL-2 production, and primary antibody production of splenic cells was much higher than previous studies involving other mice strains. AFB1 decreased the amount of circulating anti-SRBC antibody, and the helper-T cell and B cell populations in phenotyping splenic lymphocytes. There were no significant changes in natural killer cell activity, mixed lymphocyte response, hypothalamic biogenic amine concentrations, and corticotropin releasing factor, and of adrenocorticotropic hormone and corticosterone in plasma. Results were confirmed using adrenalectomized mice. The hypothalamic-pituitary-adrenal axis does not appear to have a major role in AFB1-induced immunotoxicity.