Stimpson S A, Dalldorf F G, Otterness I G, Schwab J H
Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill 27599.
J Immunol. 1988 May 1;140(9):2964-9.
The arthropathic activity of mouse recombinant IL-1 (mrIL-1) after intraarticular (i.a.) injection into rat ankles was investigated. Nanogram quantities of either mrIL-1 alpha or mrIL-1 beta induced an acute transient arthritis. Arthritis induced by i.a. mrIL-1 developed more rapidly and was more severe in ankles previously injured by i.a. injection of group A streptococcal peptidoglycan-polysaccharide (PG-APS) fragments. In addition, a protracted pain response, as judged by severe limping, occurred 60 to 90 min after mrIL-1 injection into joints previously injured by PG-APS or 4 to 6 h after mrIL-1 injection into naive joints. The severity of arthritis was related to the mrIL-1 dose. Arthropathic activity of mrIL-1 alpha was neutralized by goat anti-mouse IL-1 alpha IgG, and the activity of both the alpha and beta preparations was heat labile. Repeated episodes of acute inflammation were induced by repeated i.a. injection of mrIL-1. In naive ankles this led to chronic synovitis without histologic evidence of erosions. However, in joints previously injured by PG-APS, repeated mrIL-1 injection induced a more severe chronic synovitis with a 50% incidence of early pannus formation and limited marginal erosions of cartilage and subchondral bone. Thus, mrIL-1 induces an acute exacerbation of arthritis in joints previously injured by PG-APS and repeated exposure of these joints to mrIL-1 promotes chronic erosive synovitis. These studies provide evidence for an in vivo function of IL-1 and are consistent with its role as one of the mediators in the local regulation of inflammation in recurrences of arthritis induced by bacterial cell wall polymers.
研究了小鼠重组白细胞介素-1（mrIL-1）关节腔内注射到大鼠踝关节后的致关节炎活性。纳克量的mrIL-1α或mrIL-1β均可诱发急性短暂性关节炎。关节腔内注射mrIL-1所诱发的关节炎发展更快，在先前经关节腔内注射A组链球菌肽聚糖-多糖（PG-APS）片段损伤的踝关节中更为严重。此外，将mrIL-1注射到先前经PG-APS损伤的关节后60至90分钟，或注射到未损伤关节后4至6小时，会出现严重跛行所判断的持续性疼痛反应。关节炎的严重程度与mrIL-1剂量有关。山羊抗小鼠IL-1α IgG可中和mrIL-1α的致关节炎活性，α和β制剂的活性均对热不稳定。关节腔内反复注射mrIL-1可诱发反复的急性炎症发作。在未损伤的踝关节中，这会导致慢性滑膜炎，但无侵蚀的组织学证据。然而，在先前经PG-APS损伤的关节中，反复注射mrIL-1会诱发更严重的慢性滑膜炎，早期血管翳形成的发生率为50%，软骨和软骨下骨出现有限的边缘侵蚀。因此，mrIL-1可诱发先前经PG-APS损伤的关节中关节炎的急性加重，这些关节反复暴露于mrIL-1会促进慢性侵蚀性滑膜炎。这些研究为IL-1的体内功能提供了证据，并与其作为细菌细胞壁聚合物诱发的关节炎复发中局部炎症调节介质之一的作用相一致。
