Role of Endogenous Tumor Necrosis Factor Alpha and Gamma Interferon in Resistance to Corynebacterium pseudotuberculosis Infection in Mice

The production and roles of endogenous tumor necrosis factor alpha (TNF‐α) and gamma interferon (IFN‐γ) in the infection of Corynebacterium ( C .) pseudotuberculosis were investigated in mice. The maximum levels of TNF‐α and IFN‐γ were detected on day 4 after infection. The administration of anti‐TNF‐α monoclonal antibody (mAb) as well as anti‐IFN‐γ mAb increased bacterial proliferation in the organs, leading to the death of infected mice, but anti‐IFN‐γ mAb showed a less marked effect than anti‐TNF‐α mAb. The suppressive effect of anti‐TNF‐α and anti‐IFN‐γ mAbs on anticorynebacterial resistance was augmented by the simultaneous administration of these antibodies. Anti‐TNF‐α mAb was found to be highly effective when administered on day 0 and day 4, suggesting that TNF‐α produced during the early stage of infection is critical for the generation of resistance. Histologically, many microabscesses, severe follicular swelling and lymphocyte destruction were observed in mice treated with anti‐TNF‐α or anti‐IFN‐γ mAb. Injection of anti‐CD4 or anti‐CD8 mAb also resulted in significantly increased mortality and a marked suppression of IFN‐γ production, but had no effect on TNF‐α production. Carrageenan also showed a marked effect on the exacerbation of infection. Taken together, these results suggest that endogenously produced TNF‐α and IFN‐γ are both essential to the host defense against C. pseudotuberculosis infection and that these cytokines may have an additive effect.