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

J Rheumatol. 1996 May;23(5):878-82.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthritis, Infectious / drug therapy*
  • Arthritis, Infectious / pathology
  • Cartilage, Articular / drug effects
  • Cartilage, Articular / pathology
  • Chronic Disease
  • Disease Models, Animal
  • Inflammation / drug therapy
  • Injections, Intra-Articular
  • Joints / drug effects
  • Joints / pathology
  • Myxoma virus*
  • Rabbits
  • Serine Proteinase Inhibitors / therapeutic use*
  • Serpins / administration & dosage
  • Serpins / pharmacology
  • Serpins / therapeutic use*
  • Synovial Fluid / cytology
  • Synovial Fluid / drug effects
  • Synovial Membrane / drug effects
  • Synovial Membrane / pathology
  • Synovitis / pathology
  • Viral Proteins / administration & dosage
  • Viral Proteins / pharmacology
  • Viral Proteins / therapeutic use*

Substances

  • Serine Proteinase Inhibitors
  • Serpins
  • Viral Proteins