Gender-dependent immunosuppression following subacute exposure to fumonisin B1

The effects of fumonisin B1 (FB1), a mycotoxin produced by Fusarium lertcillioides, on the immune system are controversial; FB1 exposure causing immunosuppression in poultry, swine, bovine and rodents species and immunostimulation in rodent species. The current study was conducted to examine the effects of FB1 on the immune system of BALB/c mice and to determine if there is sex specificity. Female and male mice (five per group) received five daily subcutaneous (s.c.) injections of 2.25 mg/kg/day of FB1, on the following day tissues were collected for immunological examinations. FB1 treatment dramatically reduced relative spleen and thymus weights in females, whereas there was no effect on organ weights in males. Exposure to FB1 reduced splenic cellularity and the basal rate of lymphocyte proliferation in females only. In addition, phytohemagglutinin (PHA-P)-induced T-lymphocyte and LPS-induced B-lymphocyte proliferation were reduced in female mice. Splenocytes from female mice exposed to FB1 showed a reduced expression of interleukin-2 mRNA. These changes occurred in the absence of alterations in tumor necrosis factor alpha or interleukin-1beta mRNA expression. Phenotypic analysis indicated that FB treatment caused a relative increase in the T-lymphocyte population in the spleen of female mice only. In contrast, FB1 dramatically reduced the immature CD4+/CD8+ double positive cell population in the thymus of females. No changes were evident in the thymocyte populations of male mice treated with FB1. The results of this study indicate that FB1 is immunosuppressive in mice; the magnitude of FB1-induced immunosuppression is highly dependent on sex, females being more susceptible than males.