The beneficial effect of interleukin‐12 on arthritis induced by group B streptococci is mediated by interferon‐γ and interleukin‐10 production

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Abstract
Objective: To assess the effect of interleukin‐12 (IL‐12) administration on the evolution of systemic infection and septic arthritis induced by group B streptococci (GBS) in mice.Methods: CD1 mice were inoculated intravenously with arthritogenic strain 1/82 of type IV GBS. Exogenous murine IL‐12 was administered intraperitoneally 18 hours or 5 days after infection with 1 × 107 GBS, at doses ranging from 0.5 to 2.5 μg per mouse. Mice were monitored daily for survival and for signs of arthritis. In a subsequent set of experiments, mice were killed at selected times for examination of bacterial clearance, histopathologic changes in the joints, and cytokine production.Results: IL‐12 administration before the onset of clinical signs had a beneficial effect on GBS‐induced arthritis and was clearly dose‐dependent. The 2.5‐μg dose per mouse totally prevented death from GBS‐induced arthritis. The decrease in pathology was associated with a reduction of the bacterial burden and a change in the cytokine profile. In particular, systemic and joint levels of interferon‐γ (IFNγ) and IL‐10 significantly increased in mice treated with IL‐12, whereas a decrease in IL‐6 and IL‐1β production was observed. The beneficial effects of IL‐12, in terms of the incidence and severity of articular lesions, were reversed by coadministration of anti‐IFNγ or anti–IL‐10–neutralizing antibodies.Conclusion: The findings of this study demonstrate that IL‐12 is important in controlling the cytokine production that leads to the evolution of GBS‐induced experimental arthritis. The amelioration of articular lesions is mostly attributable to IL‐12–induced IFNγ, but with a relevant participation of IL‐12–induced IL‐10.