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Evaluation of Citrinin Toxicity on the Immune Functions of Mice 1
R V Reddy1, M J Taylor1, R P Sharma1
1Toxicology Program, Department of Animal, Dairy and Veterinary Sciences, Utah State University, Logan, Utah 84322-5600.
Abstract:
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.
Insights
Citrinin, a fungal toxin found in food, may mildly stimulate the immune system in mice. However, it did not show consistent immunotoxic effects at tested doses, despite causing kidney enlargement.
Area of Science:
- Mycology
- Immunology
- Toxicology
Background:
- Citrinin is a nephrotoxic fungal metabolite from Penicillium and Aspergillus species.
- It contaminates food sources for humans and animals, raising health concerns.
Purpose of the Study:
- To investigate the potential immunomodulatory and immunotoxic effects of citrinin.
- To assess citrinin's impact on the immune system in a mouse model.
Main Methods:
- Male CD-1 mice were administered varying doses of citrinin intraperitoneally every other day for 2-4 weeks.
- Splenic lymphocytes were cultured with mitogens (PHA, PWM, LPS) to assess proliferation.
- Antibody production and delayed hypersensitivity reactions were measured in response to sheep red blood cells (SRBC).
- In vitro cytotoxicity of citrinin on splenic lymphocytes was evaluated.
Main Results:
- Citrinin exposure led to kidney enlargement but did not affect body or organ weights or food consumption.
- Splenic lymphocyte proliferation was stimulated by citrinin.
- Antibody production against SRBC increased in mice treated with higher citrinin doses.
- Delayed hypersensitivity reactions were unaffected by citrinin.
- In vitro, high concentrations of citrinin (>1 × 10-5M) were cytotoxic to splenic lymphocytes.
Conclusions:
- Citrinin exhibits mild immunostimulatory properties in mice.
- The compound did not demonstrate consistent immunotoxic effects at the tested doses.
- Further research may be needed to fully elucidate citrinin's complex interactions with the immune system.
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