An IFN-γ-independent proinflammatory role of IL-18 in murine streptococcal cell wall arthritis

IL-18 is a member of the IL-1 family of proteins that exerts proinflammatory effects. It was formally known as IFN-gamma -inducing factor and is a pivotal cytokine for the development of Th1 responses. Apart from Th1 immune-stimulatory activity, IL-18 induces the production of proinflammatory cytokines such as TNP-alpha and IL-1 in vitro. The goal was to investigate the role of endogenous IL-18 in murine streptococcal cell wall (SCW)-induced arthritis. Furthermore, we investigated whether IL-18 neutralization had an impact on local TNF and IL-1 production. C57BL/6, BALB/c, and IFN-gamma -deficient mice were injected with 2 mg of rabbit anti;murine IL-18 Abs shortly before induction of arthritis by intra-articular injection of 25 mug of SCW fragments into the right knee joint. Suppression of joint swelling,vas noted on days 1 and 2 of SCW arthritis after blockade of endogenous IL-18. Analysis of Local cytokine concentrations showed that IL-18, TNF-alpha, and IL-1 beta levers were decreased. severe inhibition of chondrocyte proteoglycan synthesis was seen in the vehicle-treated central animals, whereas a reversal of the inhibition of chondrocyte proteoglycan synthesis was found in the anti-IL-18-exposed animals, Blockade of endogenous IL-18 in IFN-gamma deficient mice showed results similar to those found in wild-type animals, identifying a role for IL-18 that is IFN-gamma independent. The present study indicates that IL-18 is a proinflammatory cytokine during the onset of murine SCW arthritis, and this inflammatory role of IL-18 is IFN-gamma independent.