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 g 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-g dose per mouse totally prevented death from GBSinduced 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- (IFN) and IL-10 significantly increased in mice treated with IL-12, whereas a decrease in IL-6 and IL-1 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-IFN 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 IFN, but with a relevant participation of IL-12–induced IL-10.
The beneficial effect of interleukin-12 on arthritis induced by group B streptococci is mediated by interferon-gamma and interleukin-10 production.
PULITI, Manuela;BISTONI, Francesco;MOSCI, Paolo;TISSI, Luciana
2002
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 g 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-g dose per mouse totally prevented death from GBSinduced 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- (IFN) and IL-10 significantly increased in mice treated with IL-12, whereas a decrease in IL-6 and IL-1 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-IFN 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 IFN, but with a relevant participation of IL-12–induced IL-10.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
