Activation of rat splenic macrophage and lymphocyte functions by fumonisin B1

Abstract

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 B₁, on rat splenic macrophage and lymphocyte functions. Pretreatment (24 h) of resident macrophages with fumonisin B₁ (1, 10, and 100 μg/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 B₁ (1 and 10 μg/ml) and IFN-γ acted in an additive manner to activate nitric oxide production. The response of IFN-γ (50 U/ml)-activated macrophages (1.68 nmol nitrite/well) was potentiated (3.52, 4.96, and 4.44 nmol nitrite/well) by fumonisin B₁ (1, 10, and 100 μg/ml, respectively). In addition, fumonisin B₁ significantly (p<0.05) potentiated Con A (1.25 to 5 μg/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 B₁: it induces nitric oxide production by macrophages and it stimulates T cell proliferation.