Effect of the C3a-receptor antagonist SB 290157 on anti-OVA polyclonal antibody-induced arthritis

It was investigated whether the c3a-receptor antagonist (c3ara) sb 290157 was involved in the suppression of anti-ova pab-induced arthritis because it is well known that anaphylatoxin c3a plays a crucial role in the development of an effective inflammatory response during complement activation. anti-ova pab-induced arthritis was induced in dba/1j mice by administration of anti-ova pab 0.5 h prior to intra-articular (i.a.) injection of ova (0 h). two peaks of joint swelling were observed at 0.5 and 3 h. the role of c3ara in arthritis was investigated by injection of sb 290157 at concentrations of 10 and 30 mg/kg at 0 and 2 h. the antagonist was able to reduce joint swelling only at 3 h,and about 50% inhibition of joint swelling was observed with the concentration of 30 mg/kg. the c3 level was significantly decreased at 3 h compared with naïve mice showing complement consumption. furthermore,the c3 activation was observed and increased corresponding to the graded concentration of anti-ova pab. the results also revealed that the c3ara was able to reduce the expression of il-1 β in synovial tissue. taken together,the results suggested that c3ara may be effective in the inhibition of arthritis. ©2010 the japanese pharmacological society.