The effects of treatment with interleukin-1 receptor antagonist on the inflamed synovial membrane in rheumatoid arthritis.
OBJECTIVE
To evaluate the effects of treatment with interleukin-1 receptor antagonist (IL-1Ra) on synovial tissue in rheumatoid arthritis (RA).


METHODS
Twelve patients with RA entering a randomized clinical trial of human recombinant IL-1Ra underwent synovial biopsies before and after treatment. Cellular infiltration and adhesion molecule expression were evaluated after immunohistochemical staining.


RESULTS
There was a notable reduction in intimal layer macrophages and subintimal macrophages and lymphocytes after treatment with IL-1Ra at 150 mg/day (n=3). Increased cellular infiltration was observed in all patients receiving placebo (n=3); variable changes were observed after IL-1Ra 30 mg/day (n=6). In a limited study of adhesion molecule expression, down-regulation of E-selectin and vascular cell adhesion molecule-1 was observed after treatment with IL-1Ra 150 mg/day, but not after IL-1Ra 30 mg/day or placebo. The apparent arrest of progressive joint damage seen in four patients after treatment with IL-1Ra was associated with reduced intimal layer macrophage accumulation in all patients.


CONCLUSIONS
Treatment of RA with IL-1Ra resulted in reduced mononuclear cell infiltration of synovial membrane, which may represent the in vivo inhibition of biologically relevant IL-1ss-mediated pathogenic effects.
Cunnane
G
G
Department of Rheumatology, St Vincent's University Hospital, Dublin 4, Ireland.
Madigan
A
A
Murphy
E
E
FitzGerald
O
O
Bresnihan
B
B
D000293:Adolescent; D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000150:complications* / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D005260:Female; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007963:Leukocytes, Mononuclear / Q000502:physiology; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D011859:Radiography; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors*; D011994:Recombinant Proteins / Q000627:therapeutic use; D012795:Sialoglycoproteins / Q000627:therapeutic use*; D013585:Synovitis / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000473:pathology
D015815:Cell Adhesion Molecules; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins; D012795:Sialoglycoproteins