Evaluation of Citrinin Toxicity on the Immune Functions of Mice

Citrinin, a nephrotoxic fungal metabolite produced by several species of Penicillium and Aspergillus , has been found to contaminate foods used by humans and animals. The present study investigated potential effects of this compound on the immune system. Male CD-1 mice received 0, 0.12, 0.6 or 3.0 mg of citrinin/kg i.p. every other day for 2-4 weeks. Food consumption and body or organ weights were not affected but kidneys were enlarged. Splenic cells from mice exposed to citrinin for 2 or 4 weeks were cultured with or without the mitogens, phytohemagglutinin (PHA), pokewecd mitogen (PWM) or lipopolysaccharide (LPS). Exposure to citrinin stimulated splenic lymphocyte proliferation. Antibody production by splenic cells in animals sensitized to sheep red blood cells (SRBC) increased in the two highest dose groups. Delayed hypersensitivity reaction, measured as a foot-pad swelling, in response to SRBC sensitization and subsequent challenge were not affected by citrinin treatment. In vitro addition of citrinin (>1 × 10-5M) to splenic lymphocytes was cytotoxic. These findings suggest that citrinin mildly stimulates the immune system but does not have consistent immunotoxic effects at the doses tested.