Amelioration of antigen induced arthritis in rabbits treated with a secreted viral serine proteinase inhibitor.

OBJECTIVE: To evaluate the effects of intraarticular administration of SERP-1 protein, a myxoma virus derived antiinflammatory serine protease inhibitor, in an antigen induced arthritis (AIA) model of chronic inflammation.
METHODS: AIA was induced in a single joint of 15 rabbits after intraarticular (i.a.) injection of ovalbumin in animals previously immunized to the same agent administered in complete Freund's adjuvant. A 2nd i.a. injection of ovalbumin was given 2 weeks later preceded by 2 daily injections of human transforming growth factor-beta 2. SERP-1 was given by i.a. injection at 2 and 4 weeks after the last i.a. injection of ovalbumin. Three synovial specimens per joint were obtained for synovial histology. Patellar articular cartilage was assessed for collagen integrity and proteoglycan staining.
RESULTS: Synovial histology revealed significant diminution in synovial lining cellular hyperplasia, chronic inflammatory infiltration, and cartilage erosion in treated animals, particularly in those receiving 2 i.a. injections of 1 ng of SERP-1. Preservation of articular cartilage was concomitantly noted in treated animals. A dose-response influence on histopathologic change was discernible.
CONCLUSION: A viral derived antiinflammatory protein, SERP-1, demonstrates considerable potency in ameliorating chronic inflammation in the AIA model and warrants further investigation as a potential anti-arthritic agent.