McKay Anne, Leung Bernard P, McInnes Iain B, Thomson Neil C, Liew Foo Y
Division of Immunology, Infection, and Inflammation, Section of Respiratory Medicine, University of Glasgow, Glasgow, United Kingdom.
J Immunol. 2004 Mar 1;172(5):2903-8. doi: 10.4049/jimmunol.172.5.2903.
Statins, the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors, are effective serum cholesterol-lowering agents in clinical practice, and they may also have anti-inflammatory properties. Asthma is characterized by chronic eosinophilic inflammation in the airways, which is thought to be regulated by the activity of T lymphocytes. We therefore examined the anti-inflammatory activity of simvastatin in a murine model of allergic asthma. In mice previously sensitized to OVA, simvastatin treatment, either orally or i.p., reduced the total inflammatory cell infiltrate and eosinophilia in bronchoalveolar lavage fluid in response to inhaled OVA challenge. Simvastatin therapy i.p. was also associated with a reduction in IL-4 and IL-5 levels in bronchoalveolar lavage fluid and, at higher doses, a histological reduction in inflammatory infiltrates in the lungs. OVA-induced IL-4, IL-5, IL-6, and IFN-gamma secretion was reduced in thoracic lymph node cultures from simvastatin-treated mice. Simvastatin treatment did not alter serum total IgE or OVA-specific IgG1 and IgG2a levels. These data demonstrate the therapeutic potential of statin-sensitive pathways in allergic airways disease.
他汀类药物，即3-羟基-3-甲基戊二酰辅酶A还原酶抑制剂，是临床实践中有效的血清胆固醇降低药物，它们可能还具有抗炎特性。哮喘的特征是气道中的慢性嗜酸性粒细胞炎症，这种炎症被认为受T淋巴细胞活性的调节。因此，我们在过敏性哮喘小鼠模型中研究了辛伐他汀的抗炎活性。在先前对卵清蛋白（OVA）致敏的小鼠中，口服或腹腔注射辛伐他汀治疗，可减少吸入OVA激发后支气管肺泡灌洗液中的总炎症细胞浸润和嗜酸性粒细胞增多。腹腔注射辛伐他汀治疗还与支气管肺泡灌洗液中白细胞介素-4（IL-4）和白细胞介素-5（IL-5）水平的降低有关，并且在较高剂量时，肺部炎症浸润的组织学表现有所减轻。在辛伐他汀治疗的小鼠的胸段淋巴结培养物中，OVA诱导的IL-4、IL-5、IL-6和干扰素-γ（IFN-γ）分泌减少。辛伐他汀治疗未改变血清总免疫球蛋白E（IgE）或OVA特异性免疫球蛋白G1（IgG1）和免疫球蛋白G2a（IgG2a）水平。这些数据证明了他汀类药物敏感途径在过敏性气道疾病中的治疗潜力。
