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Immunosuppressive effects of dietary wortmannin on rats and mice
R Gunther1, P N Kishore, H K Abbas
1Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis 55455.
Abstract:
In order to assess the effects of the fungal toxin wortmannin on the immune system, rats and mice were fed wortmannin-containing cultures of Fusarium oxysporum for 1 or 2 weeks. Wortmannin caused significant decreases in thymic weight, thymic lymphocyte numbers, serum IgG and IgM levels, the primary humoral response to T-dependent and T-independent antigens and the proliferative response of spleen cells to pokeweed mitogen. In vitro administration of wortmannin did not produce evidence of cytotoxicity to spleen or thymus cells. The data indicate that wortmannin inhibits immune function in rats and mice and suggest that metabolic modification of the toxin is necessary for toxicity.
Insights
The fungal toxin wortmannin suppresses immune function in rats and mice, significantly reducing thymus size and lymphocyte counts. This immunosuppression suggests wortmannin
Area of Science:
- Immunology
- Toxicology
- Mycology
Background:
- Fungal toxins can impact host immune responses.
- Wortmannin is a known mycotoxin produced by Fusarium oxysporum.
- The specific immunomodulatory effects of wortmannin require further investigation.
Purpose of the Study:
- To evaluate the effects of wortmannin on the mammalian immune system.
- To determine if wortmannin exposure leads to immunosuppression in vivo.
- To assess the cytotoxicity of wortmannin on immune cells in vitro.
Main Methods:
- Rats and mice were orally administered wortmannin-containing Fusarium oxysporum cultures for one to two weeks.
- Immune organ weights (thymus) and cellularity (thymic lymphocytes) were measured.
- Serum immunoglobulin levels (IgG, IgM) and antibody responses to antigens were assessed.
- In vitro assays examined the direct cytotoxicity of wortmannin on spleen and thymus cells.
Main Results:
- Wortmannin exposure significantly decreased thymic weight and lymphocyte numbers.
- Serum IgG and IgM levels were reduced following wortmannin administration.
- Humoral immune responses to both T-dependent and T-independent antigens were impaired.
- Spleen cell proliferation in response to pokeweed mitogen was diminished.
- In vitro studies showed no direct cytotoxic effects of wortmannin on immune cells.
Conclusions:
- Wortmannin demonstrably inhibits key aspects of immune function in rodents.
- The observed immunosuppression occurs without direct cellular toxicity in vitro.
- Metabolic activation or modification of wortmannin may be required for its in vivo immunotoxicity.