Activation of rat splenic macrophage and lymphocyte functions by fumonisin B1

Fumonisins represent a family of toxic, structurally related metabolites produced by fungi that are found in corn worldwide. We investigated the effects of the mycotoxin, fumonisin B-1, on rat splenic macrophage and lymphocyte functions. Pretreatment (24 h) of resident macrophages with fumonisin B-1 (1, 10, and 100 mu g/ml) significantly (p < 0.01) stimulated nitric oxide production (0.48, 2.60, and 4.40 nmol nitrite/well, respectively), compared with the response of untreated macrophages (no nitrite detected), after 72 h of culture. Fumonisin B-1 (1 and 10 mu g/ml) and IFN-gamma acted in an additive manner to activate nitric oxide production. The response of IFN-gamma (50 U/ml)-activated macrophages (1.68 nmol nitrite/well) was potentiated (3.52, 4.96, and 4.44 nmol nitrite/well) by fumonisin B-1 (1, 10, and 100 mu g/ml, respectively). In addition, fumonisin B-1 significantly (p < 0.05) potentiated Con A (1.25 to 5 mu g/ml) (1.46- to 2.62-fold increases)- and antiTCR, IL-2 or antiTCR + IL-2 (1.72- to 2.60-fold increases)-induced proliferation of splenic cells in the presence of the nitric oxide synthase inhibitor N-G-monomethyl-L-arginine (NMA). These results show two distinct and separate effects of fumonisin B-1: it induces nitric oxide production by macrophages and it stimulates T cell proliferation. Published by Elsevier Science B.V.