Date of Award:

5-1995

Document Type:

Dissertation

Degree Name:

Doctor of Philosophy (PhD)

Department:

Animal, Dairy, and Veterinary Sciences

Department name when degree awarded

Toxicology

Committee Chair(s)

Reed P. Warren

Committee

Reed P. Warren

Committee

Stan D. Allen

Committee

Howard M. Deer

Abstract

Aflatoxin B1 and T-2 toxin are mycotoxins, which produce their immunotoxic effects by affecting nonspecific and acquired immunity in different species. The mechanisms of their immunotoxicity are still obscure. Cytokines are the key signaling molecules during the immune response. In this study, expression of macrophage-produced cytokines Interleukin-lα (IL-lα), tumor necrosis factor (TNF), and IL-6, and lymphocyte-produced cytokines IL-2, interferon y (IFNy), and IL-3 was measured at the mRNA and protein levels, after in vitro activation with mitogens in AFB1-and T-2-toxin-exposed mice.

Significant changes in the organ weights, especially in the mice exposed to a high dose of T-2 toxin, and no effect in AFB1-exposed mice were observed.

ConA-induced production of IL-2, IFNy, and IL-3 mRNA and protein levels in AFB1-exposed mice showed a decrease in low dose groups (significant for IL-2 mRNA), but no change at other doses. However, in T-2-toxin-treated animals, there was a significant induction of IL-2 and IFNy mRNA in high and low doses and of IL-3 mRNA at the medium dose. The protein levels of IL-2 and IFNy did not follow the mRNA levels in high dose and the protein levels of IL-3 were significantly increased in medium and low doses.

LPS-induced IL-lα and TNF mRNA and protein levels in AFB1-exposed mice were suppressed at the high dose while mRNA levels of both cytokines were increased significantly in the low and medium doses. Low and medium doses of AFB1 also significantly decreased IL-lα protein levels and the high dose decreased IL-6 protein. In T-2 toxin-treated mice, no significant difference in mRNA levels of these cytokines was observed but a general pattern of significant suppression of their protein levels (except IL-lα at medium dose) showed that both toxins regulate the cytokine expression differently.

Based on the above discussed results and others, AFB1 may alter cell-mediated immunity by affecting the communication between macrophages and T lymphocytes through inhibiting the macrophage-producing cytokines. T-2 toxin-induced immunosuppression may be due not only to the inhibition of macrophage-producing cytokines, but also to the lack of effector cells to respond to the cytokines (IL-2, IFNy, and IL-3).

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