Alteration of major cytokines produced by mitogen-activated peritoneal macrophages and splenocytes in T-2 toxin-treated male CD-1 mice.

Fusarium T-2 toxin has immunotoxic properties that may be related to the modulation of cytokine expression by cells of the immune system. Male CD-1 mice were used to study the effect of in vivo exposure to T-2 toxin on the alteration of interleukin (IL)-1α, tumor necrosis factor α (TNF), and IL-6 in lipopolysaccharide-stimulated peritoneal macrophages, and IL-2, IL-3, and interferon γ (IFNγ) in concanavalin A (Con A)-stimulated splenocytes. Mice were orally dosed with 0, 0.1, 0.5, and 2.5 mg T-2 toxin/kg body weight for 2 weeks on alternate days. Northern blot analysis of IL-1α, TNF, and IL-6 mRNA from activated peritoneal macrophages showed no significant differences between control and treated groups. Measurements of secreted protein by immunoassay demonstrated suppression of these cytokines in all treated groups, suggesting that T-2 toxin affects the translational or post-translational regulation of these cytokines from peritoneal macrophages. Levels of IL-2, IL-3, and IFNγ mRNA from Con A-activated splenocytes were higher in all treated groups. The increases were significant for IL-2 and IFNγ in the groups receiving low (0.1 mg/kg) and high (2.5 mg/kg) doses of T-2 toxin, and for IL-3 in the group receiving a medium (0.5 mg/kg) dose of this toxin (P ≤ 0.05). Results indicated that T-2 toxin given orally at low or medium doses induces transcription or increases mRNA stability of IL-2, IFNγ, and IL-3. Protein levels of all three cytokines were also increased, indicating that T-2 toxin also increases translational/post-translational efficiency of IFNγ, IL-2, and IL-3. Possible mechanisms in the immunosuppressive effects of T-2 toxin may involve endotoxemia resulting after the toxin administration, alteration of the stability of mRNA, or previously described effects of T-2 toxin on protein synthesis.