Yamagata Toshiaki, Kinoshita Koji, Nozaki Yuji, Sugiyama Masafumi, Ikoma Shinya, Funauchi Masanori
Department of Nephrology and Rheumatology, Kinki University School of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511, Japan.
Rheumatol Int. 2007 May;27(7):631-9. doi: 10.1007/s00296-006-0270-9. Epub 2006 Nov 21.
Here we evaluated whether 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have beneficial effects for collagen-induced arthritis (CIA). DBA/1 mice were immunized with bovine type-II collagen and administered 100 mg/kg of pravastatin interperitoneally. We measured the effects of pravastatin for CIA including infiltration of macrophages at the synovial membrane and production of anti-type-II collagen antibodies and cytokines. Adverse reactions of pravastatin were also measured. The pravastatin-treated mice had delayed onset of CIA compared with the controls. The involvement of inflammatory cells in the synovial membrane and the expression of monocyte chemotactic protein-1 (MCP-1) mRNA in the joint were reduced. Moreover, some cytokines (TNF-alpha, IL-6, IFN-gamma) and MCP-1 levels in the supernatants of spleen cells cultured with pravastatin decreased. Meanwhile, adverse reactions of pravastatin, such as peritonitis, were not detected. Pravastatin may have good prospects for treating some anti-inflammatory effects on human rheumatoid arthritis.
在此,我们评估了3-羟基-3-甲基戊二酰辅酶A还原酶抑制剂(他汀类药物)对胶原诱导性关节炎(CIA)是否具有有益作用。用牛II型胶原免疫DBA/1小鼠,并腹腔注射100mg/kg普伐他汀。我们测定了普伐他汀对CIA的影响,包括滑膜巨噬细胞浸润、抗II型胶原抗体和细胞因子的产生。还测定了普伐他汀的不良反应。与对照组相比,普伐他汀治疗的小鼠CIA发病延迟。滑膜中炎性细胞的参与以及关节中单核细胞趋化蛋白-1(MCP-1)mRNA的表达减少。此外,用普伐他汀培养的脾细胞上清液中一些细胞因子(肿瘤坏死因子-α、白细胞介素-6、干扰素-γ)和MCP-1水平降低。同时,未检测到普伐他汀的不良反应,如腹膜炎。普伐他汀在治疗人类类风湿关节炎的某些抗炎作用方面可能具有良好的前景。