Influence of interferon-gamma administration on the severity of experimental group B streptococcal arthritis

To assess the effect of interferon-gamma (IFNgamma) administration on the evolution of systemic infection and septic arthritis induced by group B streptococci (GBS) in mice.

CD1 mice were inoculated intravenously with arthritogenic strain 1/82 of type IV GBS. Exogenous murine IFNgamma or anti-IFNgamma monoclonal antibodies were administered intravenously either 2 hours (-2 hours) before or 18 hours after infection with 1 x 10(7) GBS. 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, joint histopathology, and cytokine production.

Mortality in mice treated with IFNgamma at -2 hours was 100%, compared with 20% in those treated at 18 hours and with 40% in controls. As indicated by the arthritis score, mice treated with IFNgamma at -2 hours developed early and more severe arthritis, whereas those treated at 18 hours had milder arthritis compared with infected controls. Less severe joint pathology in the mice treated with IFNgamma at 18 hours correlated with low levels of interleukin-6 (IL-6) and IL-1beta and a low bacterial load in the joints, whereas rapid onset and worsening of articular lesions in those treated at -2 hours corresponded to early and sustained levels of IL-6.

The findings of this study demonstrate that the effects mediated by IFNgamma on GBS-induced arthritis may be detrimental or beneficial, depending on the time of administration of IFNgamma in relation to infection with the antigen.