AMELIORATION OF ESTABLISHED COLLAGEN-INDUCED ARTHRITIS (CIA) WITH ANTI-IL-1

Inflammatory cytokines have been implicated in the pathogenesis of rhe umatoid arthritis (RA). To investigate the role of interleukin-l (IL-1 ) and tumor necrosis factor alpha (TNF alpha) in arthritic processes w e studied the effect of neutralizing antibodies against murine IL-1 an d TNF alpha in murine collagen-induced arthritis (CIA). Combined i.p. injection of anti-IL-1 alpha and anti-IL-1 beta (anti-IL-1 alpha,beta) , given before onset of the disease, completely prevented CIA, In cont rast, treatment with anti-TNF alpha at this time point only delayed th e onset of arthritis. Remarkably, a single injection of anti-IL-1 alph a,beta was also highly effective in suppressing established arthritis, reducing both inflammation and cartilage destruction. Suppression was most pronounced with the combination of anti-IL-1 alpha and beta, but anti-IL-1 beta alone also gave significant relief. Specific antibodie s against TNF alpha had no effect on established CIA. Of interest, ant i-IL-1 alpha,beta treatment started after onset of CIA completely norm alized chondrocyte synthetic function, which was highly suppressed in the non-treated group. It is concluded that IL-1 and TNF alpha are imp ortant cytokines during the onset of CIA and that IL-1 is the key medi ator of inflammation and cartilage damage in established CIA.