ENDOGENOUS GAMMA-INTERFERON, TUMOR-NECROSIS-FACTOR, AND INTERLEUKIN-6IN STAPHYLOCOCCUS-AUREUS INFECTION IN MICE

The production and roles of endogenous gamma interferon (IFN-gamma), t umor necrosis factor (TNF), and interleukin-6 (IL-6) in both lethal an d nonlethal infections of Staphylococcus aureus were investigated in m ite. In the case of nonlethal infection, although no bacteria were det ected in the bloodstreams, bacteria that colonized and proliferated pe rsistently for 3 weeks were found in the kidneys. All mice given letha l injections died within 7 days, and large numbers of bacteria were de tected in the bloodstreams, spleens, and kidneys. The first peaks of I FN-gamma, TNF, and IL-6 were observed in the bloodstreams and spleens of the mice with nonlethal and lethal infections within 24 h. Thereaft er, in the nonlethal cases, IFN-gamma, TNF, and IL-6 peaked again in t he spleens and kidneys during the period of maximum growth of bacteria in the kidneys, although only IL-6 was detected in the sera. In contr ast, in the case of lethal infection, the titers of IFN-gamma and IL-6 in the sera and TNF in the kidneys peaked before death. Effects of in vivo administration of monoclonal antibodies (MAbs) against IFN-gamma and TNF on the fates of S. aureus-infected mice were studied. In the nonlethal infections, anti-TNF alpha (anti-TNF-alpha) MAb-treated mice , but not anti-IFN-gamma MAb-treated mice, died as a result of worseni ng infection, suggesting that endogenous TNF plays a protective role i n host resistance to S. aureus infection. In the mice that received le thal doses, injection of anti-TNF-alpha MAb accelerated death. However , although injection of anti-IFN-gamma MAb inhibited host resistance o f the infected mice early in infection, most of the animals survived t he lethal infection by injection of anti-IFN-gamma MAb, suggesting tha t endogenous IFN-gamma plays a detrimental role in S. aureus infection . Thus, this study demonstrated that IFN-gamma and TNF play different roles in S. aureus infection.