Therapeutic efficacy of intra-articular adrenomedullin injection in antigen-induced arthritis in rabbits.
Therapeutic efficacy of intra-articular adrenomedullin injection in antigen-induced arthritis in rabbits.
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DOI：
10.1186/ar2550
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发表时间：
2008
影响因子：
4.9
通讯作者：
Chosa E
中科院分区：
文献类型：
--
作者：
Okura T;Marutsuka K;Hamada H;Sekimoto T;Fukushima T;Asada Y;Kitamura K;Chosa E
肾上腺髓质素是一种有效的血管舒张和降血压肽，也是一种主要具有抗炎作用的内源性免疫调节因子。本研究的目的是评估肾上腺髓质素对抗原诱导性关节炎兔（类风湿性关节炎的实验模型）的治疗效果。通过将卵清蛋白注射到预免疫兔的关节间隙中诱导双膝关节关节炎后，将每日剂量增加的肾上腺髓质素注射到膝关节间隙中或将生理盐水注射到对侧膝关节间隙中作为对照。对于时程实验，每天将肾上腺髓质素和盐水注射到膝关节间隙，持续 7 天和 20 天。将注射肾上腺髓质素的膝关节与对照膝关节的关节肿胀程度和组织学变化进行比较。对髌下脂肪垫和滑膜组织进行组织学评估。使用实时定量PCR测量滑膜组织中TNFα、IL-6、血管内皮生长因子和转化生长因子-β mRNA水平。每天向患有抗原诱导关节炎的兔子的膝关节间隙注射肾上腺髓质素，可以减少关节肿胀。组织学检查显示，肾上腺髓质素减少了滑膜组织中的水肿变化和炎症细胞的浸润。 mRNA水平分析显示，肾上腺髓质素以剂量依赖性方式显着降低TNFα mRNA表达21%至49%，并以剂量依赖性方式增加IL-6 mRNA表达45%至121%。这些结果表明，每天向患有抗原诱导性关节炎的兔子的膝关节间隙注射肾上腺髓质素可以改善关节炎关节的炎症反应。因此，肾上腺髓质素可用于治疗类风湿性关节炎。然而，肾上腺髓质素对滑膜组织中IL-6产生的影响可能是类风湿性关节炎治疗中的不良副作用。
Adrenomedullin is a potent vasodilatory and hypotensive peptide as well as an endogenous immunomodulatory factor with predominantly anti-inflammatory effects. The purpose of the present study was to evaluate the therapeutic effects of adrenomedullin in rabbits with antigen-induced arthritis, an experimental model of rheumatoid arthritis. Following the induction of arthritis in both knee joints by ovalbumin injection into the joint spaces of pre-immunized rabbits, increasing daily doses of adrenomedullin were injected into the knee joint spaces or saline was injected into the contralateral knee joint spaces as the control. For time-course experiments, adrenomedullin and saline were injected into the knee joint spaces daily for 7 days and 20 days. The degree of joint swelling and the histological change in the knee joints injected with adrenomedullin were compared with the control knee joints. Histological evaluation of the infrapatellar fat pads and synovial tissue was performed. TNFα, IL-6, vascular endothelial growth factor and transforming growth factor-beta mRNA levels in the synovial tissue were measured using real-time quantitative PCR. Daily injections of adrenomedullin into the knee joint spaces of rabbits with antigen-induced arthritis decreased joint swelling. Histological examination revealed that adrenomedullin reduced edematous changes and the infiltration of inflammatory cells in the synovial tissues. Analysis of mRNA levels showed that adrenomedullin significantly reduced TNFα mRNA expression by 21% to 49% in a dose-dependent manner, and dose-dependently increased IL-6 mRNA expression by 45% to 121%. These results suggest that daily injections of adrenomedullin into the knee joint spaces of rabbits with antigen-induced arthritis ameliorated the inflammatory response in arthritic joints. Adrenomedullin may thus be useful as a treatment for rheumatoid arthritis; however, the effect of adrenomedullin on IL-6 production in the synovial tissue may be an undesirable adverse effect in rheumatoid arthritis therapy.
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DOI：
10.1084/jem.179.5.1529
发表时间：
1994-05-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Mizuhara H;O'Neill E;Seki N;Ogawa T;Kusunoki C;Otsuka K;Satoh S;Niwa M;Senoh H;Fujiwara H
通讯作者：
Fujiwara H
影响因子：
--
作者：
CHU, CQ;FIELD, M;MAINI, RN
通讯作者：
MAINI, RN
影响因子：
27.4
作者：
Nishimoto, N;Kishimoto, T;Yoshizaki, K
通讯作者：
Yoshizaki, K
影响因子：
24.5
作者：
Gonzalez-Rey, E.;Fernandez-Martin, A.;Delgado, M.
通讯作者：
Delgado, M.
影响因子：
20.3
作者：
Clauss, M;Sunderkötter, C;Risau, W
通讯作者：
Risau, W