IMPACT OF INTERFERON-GAMMA RECEPTOR DEFICIENCY ON EXPERIMENTAL STAPHYLOCOCCUS-AUREUS SEPTICEMIA AND ARTHRITIS

The role of IFN-gamma in the regulation of host resistance to Staphylo coccus aureus was studied using IFN-gamma receptor-deficient (IFN-gamm a R(-/-)) mice in a model of S, aureus-induced septicemia and arthriti s, IFN-gamma R(-/-) mice and wild-type controls were inoculated intrav enously with a toxic shock syndrome toxin-l-producing S, aureus LS-1 s train, IFN-gamma R(-/-) mice displayed significantly more frequent and more severe arthritis compared with wild-type littermates (p < 0.01) throughout the course of infection, Notably, IFN-gamma R(-/-) mice dev eloped severe sepsis with high mortality early after the inoculation w ith staphylococci. However, the mortality of wild-type mice became sig nificantly higher at later stages of the disease compared with IFN-gam ma R(-/-) mice (p < 0.05), This differential outcome of sepsis-related mortality was associated with deficiencies of bacterial elimination f rom blood and parenchymatous organs and correlated well to serum level s of IL-6 and spleen IL-1 beta and TNF-beta mRNA expression, Thus, bac terial growth and proinflammatory cytokines IL-1 beta, TNF-beta, and I L-6 were higher at the early stage of infection in IFN-gamma(-/-) mice but increased at the later stage in wild-type littermates. Our data i ndicate that the absence of IFN-gamma R leads to harmful as well as be neficial effects in S, aureus infection, depending on the stage of the disease and the localization of the infection.