REGRESSION OF COLLAGEN-INDUCED ARTHRITIS WITH TAXOL, A MICROTUBULE STABILIZER

Objective. To investigate the capacity of taxol, a microtubule stabilizer, to inhibit collagen-induced arthritis (CIA), a model of rheumatoid arthritis. Methods. Louvain rats were immunized with type LI collagen (day 0) to induce arthritis. Taxol was administered beginning on day 2 (prevention protocol) or at arthritis onset on day 9 (in either a high-dose or low-dose suppression protocol). Rats were assessed clinically and radiographically for arthritis severity. Cellular and humoral immune responses to type II collagen were also evaluated. Results. Institution of taxol prior to arthritis onset completely precluded the development of CIA (P < 0.0001 versus controls). It also suppressed established clinical disease (high-dose protocol P < 0.0000001; low-dose protocol P < 0.0001) and radiographic erosions (high-dose protocol P < 0.00001; low-dose protocol P < 0.001) compared with controls, Levels of IgG antibodies, but not delayed-type hypersensitivity, to type II collagen were reduced after taxol administration. Conclusion. Taxol completely prevented the induction of CIA and caused significant regression of existing arthritis.