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. CONCLUSION: 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.
RCT Entities:
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. CONCLUSION: 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.
Authors: J J Haringman; D M Gerlag; A H Zwinderman; T J M Smeets; M C Kraan; D Baeten; I B McInnes; B Bresnihan; P P Tak Journal: Ann Rheum Dis Date: 2004-12-02 Impact factor: 19.103
Authors: M D Smith; D Baeten; A-K Ulfgren; I B McInnes; O Fitzgerald; B Bresnihan; P P Tak; D Veale Journal: Ann Rheum Dis Date: 2005-06-23 Impact factor: 19.103
Authors: Erik af Klint; Anca I Catrina; Peter Matt; Petra Neregråd; Jon Lampa; Ann-Kristin Ulfgren; Lars Klareskog; Staffan Lindblad Journal: Arthritis Res Ther Date: 2009-06-02 Impact factor: 5.156
Authors: A W R van Kuijk; D M Gerlag; K Vos; G Wolbink; M de Groot; M A de Rie; A H Zwinderman; B A C Dijkmans; P P Tak Journal: Ann Rheum Dis Date: 2008-07-22 Impact factor: 19.103