TUMOR-NECROSIS-FACTOR-ALPHA AS A CONTRIBUTOR IN FUMONISIN B-1 TOXICITY

Fumonisin B-1 is a toxic product of Fusarium moniliforme, which inhibi ts ceramide synthase, leading to accumulation of free sphingoid bases. Despite its known biochemical action, the mechanism of toxicity is no t fully understood. Male BALB/c mice were injected subcutaneously with 0 to 6.75 mg/kg/day of fumonisin B-1 for 5 days. One day after the la st treatment, spleens were collected, and peritoneal macrophages were obtained from separate groups after an intraperitoneal injection of th ioglycolate broth. Peripheral leukocyte counts were increased and kidn ey weights were decreased by fumonisin B-1 treatment. Presence of apop totic cells in the liver and kidney of treated mice was confirmed by e nzymatic immunoassay. Macrophages cultured with lipopolysaccharide ind icated an increased secretion of tumor necrosis factor-alpha (TNF-alph a) but not of interleukin-1 alpha. No effect was seen on interferon-ga mma production when splenocytes were incubated with concanavalin A. El evation of leukocyte and reticulocyte counts was abrogated by pretreat ment with anti-TNF-alpha antibody before a single dose fumonisin B-1 ( 25 mg/kg), supporting the hypothesis that the fumonisin B-1 toxicity i nvolves TNF-alpha. Cultures of J774A.1 cells, when treated with fumoni sin B-1, produced TNF-alpha in vitro. Results indicate that fumonisin B-1 toxicity may involve secretion of TNF-alpha by TNF-alpha-producing cells without altering interleukin-1 alpha or interferon-gamma. The i nfluence on TNF-alpha-production may be a contributing factor to fumon isin B-1-induced apoptosis and other observed toxic effects in animals .