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The production and role of endogenous cytokines during the course of secondary Corynebacterium (C.) pseudotuberculosis infection were investigated in mice. When immunized mice were challenged on day 28 after primary infection, tumor necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) were found to appear at 3 hr and to reach the maximum at 24 hr after challenge. Spleen cells of mice primarily infected from 2 to 8 weeks before produced a significant amount of TNF-alpha and IFN-gamma when stimulated with formalin-killed bacteria. However, they could not produce detectable amounts of IL-4. The administration of anti-TNF-alpha monoclonal antibody (MAb) and IFN-gamma MAb increased bacterial proliferation in the organs of immune mice and exacerbated the secondary infection. Injection of anti-CD4 MAb alone or anti-CD4 plus anti-CD8 MAbs resulted in significantly increased mortality and a marked suppression of bacterial elimination as well as cytokine production of secondarily infected mice, while the treatment with anti-CD8 MAb alone showed no effect on either the resistance or cytokine production of mice. These results suggest that CD4, probably Th1 T cells, play an important role for establishment of protective immunity against secondary C. pseudotuberculosis infection by secreting TNF-alpha and IFN-gamma.

The present study was performed to investigate the role of CR3, the type 3 complement receptor, in host defense against primary and secondary Corynebacterium (C.) pseudotuberculosis infection in mice. Treatment of mice with 5C6, an anti-CR3 monoclonal antibody (mAb), resulted in unrestricted multiplication of bacteria in the organs and dramatically increased mortalities of the infected mice. Histological examinations showed the inflammation, degeneration and necrosis of organs and revealed that the infection-enhancing effect of 5C6 mAb was associated with the failure of mice to focus mononuclear phagocytes at sites of bacterial multiplication. These results suggest that CR3 plays an important role in host defense against primary as well as secondary C. pseudotuberculosis infection in mice.

The production and roles of endogenous tumor necrosis factor alpha (TNF-alpha) 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 administration of anti-TNF-alpha monoclonal antibody (mAb) as well as anti-IFN-gamma mAb increased bacterial proliferation in the organs, leading to the death of infected mice, but anti-IFN-gamma mAb showed a less marked effect than anti-TNF-alpha mAb. The suppressive effect of anti-TNF-alpha and anti-IFN-gamma mAbs on anticorynebacterial resistance was augmented by the simultaneous administration of these antibodies. Anti-TNF-alpha mAb was found to be highly effective when administered on day 0 and day 4, suggesting that TNF-alpha 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-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 IFN-gamma production, but had no effect on TNF-alpha production. Carrageenan also showed a marked effect on the exacerbation of infection. Taken together, these results suggest that endogenously produced TNF-alpha and IFN-gamma are both essential to the host defense against C. pseudotuberculosis infection and that these cytokines may have an additive effect.