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

Objective. To assess the effect of interferon-gamma (IFN gamma) administrat ion 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 IFN gamma or anti-IFN gamma monoclonal antibodies were administered intravenously either 2 hours (-2 hours) befor e or 18 hours after infection with 1 x 10(7) GBS, Mice were monitored daily for survival and for signs of arthritis. Ina subsequent set of experiments , mice were killed at selected times for examination of bacterial clearance , joint histopathology, and cytokine production. Results, Mortality in mice treated with IFN gamma at -2 hours was 100%, com pared with 20% in those treated at 18 hours and with 40% in controls, As in dicated by the arthritis score, mice treated with IFN gamma at -2 hours dev eloped early and more severe arthritis, whereas those treated at 18 hours h ad milder arthritis compared with infected controls. Less severe joint path ology in the mice treated with IFN gamma at 18 hours correlated with low le vels of interleukin-6 (IL-6) and IL-1 beta and a low bacterial load in the joints, whereas rapid onset and worsening of articular lesions in those tre ated at -2 hours corresponded to early and sustained levels of IL-6, Conclusion. The findings of this study demonstrate that the effects mediate d by IFN gamma on GBS-induced arthritis may be detrimental or beneficial, d epending on the time of administration of IFN gamma in relation to infectio n with the antigen.