Mitigation of Arthritis by High-Dose Administration of a COX-2 Inhibitor in the Collagen-Induced Arthritis Model in the Mouse

Abstract

Non-steroidal anti-inflammatory drugs (NSAIDs), including selective cyclooxygenase (COX)-2 inhibitors, improve many parameters of arthritis in the adjuvant-induced arthritis model in the rat (Anderson et al., 1996). However, results with NSAIDs in the collagen-induced arthritis model in the mouse (Wooley, 1988) have been equivocal, possibly due to a mechanism that is prostaglandin-independent and because the level of dosing is limited due to gastrointestinal (GI) toxicity (Griswold et al., 1988; Phadke et al., 1985; Smith et al., 1990). With the advent of selective COX-2 inhibitors, it was possible to evaluate the efficacy of high-level dosing of a COX-2 inhibitor in the context of a GI-sparing background. The specific objectives of this study were to evaluate whether SC-046, a selective COX-2 inhibitor, mitigates the incidence and/or severity of arthritis and, possibly, is disease-modifying in the collagen-induced arthritis model in the mouse.