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

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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.