Suppression of collagen-induced arthritis with a serine proteinase inhibitor (serpin) derived from myxoma virus.
Many viruses encode virulence factors to facilitate their own survival by modulating a host's inflammatory response. One of these factors, secreted from cells infected with myxoma virus, is the serine proteinase inhibitor (serpin) Serp-1. Because Serp-1 had demonstrated anti-inflammatory properties in arterial injury models and viral infections, it was cloned and evaluated for therapeutic efficacy in collagen-induced arthritis (CIA). Clinical severity was significantly lower in the Serp-1 protocols (p<0.0001) and blinded radiographs indicated that the Serp-1 group had significantly less erosions than the controls (p<0.01). Delayed-type hypersensitivity was lower in the Serp-1 group but antibody titers to type II collagen were not significantly altered. Recipients had minimal histopathologic synovial changes and did not develop neutralizing antibodies to Serp-1. These results indicate that Serp-1 impedes the pathogenesis of CIA and suggests that the therapeutic potential of serine proteinase inhibitors in inflammatory joint diseases, such as rheumatoid arthritis, should be investigated further.
Division of Rheumatology, UCLA School of Medicine, Los Angeles, CA, USA. Electronic address: ebrahn@mednet.ucla.edu.
Ernest
E
Brahn
Division of Rheumatology, UCLA School of Medicine, Los Angeles, CA, USA.
Sarah
S
Lee
Division of Cardiovascular Medicine, University of Florida, Gainesville, FL, USA.
Alexandra
A
Lucas
Department of Molecular Genetics and Microbiology, University of Florida, Gainsville, FL, USA.
Grant
G
McFadden
Viron Therapeutics, Inc., London, Ontario, Canada.
Colin
C
Macaulay
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000097:blood / Q000276:immunology; D001169:Arthritis, Experimental / Q000000981:diagnostic imaging / Q000276:immunology / Q000517:prevention & control*; D001772:Blood Cell Count; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006968:Hypersensitivity, Delayed / Q000276:immunology / Q000517:prevention & control; D015151:Immunoblotting; D007596:Joints / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008969:Molecular Sequence Data; D009233:Myxoma virus / Q000235:genetics / Q000378:metabolism; D011859:Radiography; D051381:Rats; D011919:Rats, Inbred Strains; D015842:Serine Proteinase Inhibitors / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D015843:Serpins / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*
D000906:Antibodies; D015842:Serine Proteinase Inhibitors; D015843:Serpins; D014764:Viral Proteins
Collagen arthritis; Immunotherapy; Myxoma; Rheumatoid; Serpin