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-alp ha) and gamma interferon (IFN-gamma) in the infection of Corynebacterium (C ,) pseudotuberculosis were investigated in mice. The maximum levels of TNF- alpha and IFN-gamma were detected on day 4 after infection. The administrat ion of anti-TNF-alpha monoclonal antibody (mAb) as well as anti-IFN-gamma m Ab increased bacterial proliferation in the organs, leading to the death of infected mice, but anti-IFN-gamma mAb showed a less marked effect than ant i-TNF-alpha mAb, The suppressive effect of anti-TNF-alpha and anti-IFN-gamm a mAbs on anticorynebacterial resistance was augmented by the simultaneous administration of these antibodies. Anti-TNF-alpha mAb was found to be high ly effective when administered on day 0 and day 4, suggesting that TNF-alph a produced during the early stage of infection is critical for the generati on of resistance, Histologically, many microabscesses, severe follicular sw elling and lymphocyte destruction were observed in mice treated with anti-T NF-alpha or anti-IFN-gamma mAb, Injection of anti-CD4 or anti-CD8 mAb also resulted in significantly increased mortality and a marked suppression of I FN-gamma production, but had no effect on TNF-alpha production, Carrageenan also showed a marked effect on the exacerbation of infection, Taken togeth er, these results suggest that endogenously produced TNF-alpha and IFN-gamm a are both essential to the host defense against C, pseudotuberculosis infe ction and that these cytokines may have an additive effect.