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.


CONCLUSIONS
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.
Maksymowych
W P
WP
Department of Medicine, University of Alberta, Edmonton, Canada.
Nation
N
N
Nash
P
P
Macen
J
J
Lucas
A
A
McFadden
G
G
Russell
A S
AS
D000818:Animals; D001170:Arthritis, Infectious / Q000188:drug therapy* / Q000473:pathology; D002358:Cartilage, Articular / Q000187:drug effects / Q000473:pathology; D002908:Chronic Disease; D004195:Disease Models, Animal; D007249:Inflammation / Q000188:drug therapy; D007270:Injections, Intra-Articular; D007596:Joints / Q000187:drug effects / Q000473:pathology; D009233:Myxoma virus; D011817:Rabbits; D015842:Serine Proteinase Inhibitors / Q000627:therapeutic use*; D015843:Serpins / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D013582:Synovial Fluid / Q000166:cytology / Q000187:drug effects; D013583:Synovial Membrane / Q000187:drug effects / Q000473:pathology; D013585:Synovitis / Q000473:pathology; D014764:Viral Proteins / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
D015842:Serine Proteinase Inhibitors; D015843:Serpins; D014764:Viral Proteins