LOCAL THERAPY WITH SOLUBLE COMPLEMENT RECEPTOR-1 (SCR1) SUPPRESSES INFLAMMATION IN RAT MONOARTICULAR ARTHRITIS

Complement activation has been implicated in the pathogenesis of human rheumatoid arthritis. We sought to determine whether inhibition of co mplement (C) using sCR1 could influence the development and progressio n of antigen arthritis in the rat, a recognized model of human chronic synovitis. The effect of C inhibition, systemically and locally, on t hree different stages of disease was examined: (i) prophylaxis, (ii) t reatment of established inflammation, and (iii) prevention of antigen- induced flares of disease. Arthritis was assessed by knee swelling and by histological examination. Our results show that intra-articular in jection of sCR1 prior to disease onset reduced joint swelling and deve lopment of arthritis, whereas systemic administration was ineffective. Treatment of established arthritis with intraarticular sCR1 3 days af ter disease onset caused a transient reduction in swelling, but treatm ent 7 days after disease onset had no effect on disease. An intra-arti cular dose of sCR1 given at the time of disease flares had a small, ye t significant effect on knee swelling. We conclude that complement act ivation is important in the initiation and maintenance of inflammation in antigen arthritis. The potent effect of local C inhibition suggest s that C biosynthesis and activation within the joint contributes to i nflammation in this model of arthritis.