The dual role of interferon‐γ in experimental Staphylococcus aureus septicaemia versus arthritis

Abstract

To evaluate the role of interferon-γ (IFN-γ) in Staphylococcus aureus infection, we investigated the effects of supplementation with and neutralization of IFN-γ during septicaemia and arthritis in a murine model. In vivo administration of IFN-γ both before and after bacterial inoculation significantly decreased mortality on one hand but enhanced the development of arthritis on the other. Treatment of mice with anti-IFN-γ monoclonal antibodies (mAb) before and after bacterial inoculation did not significantly influence the survival rate but decreased the frequency and severity of arthritis. The beneficial effect of supplementation with IFN-γ on septicaemia was correlated to the increased phagocytosis and bacterial clearance from liver and kidneys. The down-regulation of the development of arthritis by anti-IFN-γ mAb was accompanied by the decreased serum tumour necrosis factor-α, interleukin-6 and interleukin-1β levels. These results demonstrate a significant role for IFN-γ in simultaneous protection against septicaemia but promotion for the development of septic arthritis.