Samson K T R, Minoguchi K, Tanaka A, Oda N, Yokoe T, Yamamoto Y, Yamamoto M, Ohta S, Adachi M
First Department of Internal Medicine, Showa University School of Medicine, Tokyo, Japan.
Clin Exp Allergy. 2006 Apr;36(4):475-82. doi: 10.1111/j.1365-2222.2006.02470.x.
Statins have anti-inflammatory effects on immune cells.
To investigate the immunomodulatory effects of fluvastatin on peripheral blood mononuclear cells (PBMCs) after allergen-specific and non-allergen-specific stimulation in patients with asthma and in healthy subjects.
PBMCs from seven patients with asthma who showed elevated immunoglobulin (Ig)E to house dust mite were isolated and stimulated with Dermatofagoides farinae, purified protein derivative, and phytohaemagglutinin (PHA) in the presence or absence of fluvastatin. PBMCs from seven healthy subjects were stimulated with PHA. The effects of fluvastatin on cell proliferation and production of cytokines (interferon [IFN]-gamma and interleukin [IL]-5) and chemokines (chemokine CXC motif, ligand [CXCL10], and CC chemokine ligand [CCL17]) were measured. Migration of T helper (Th)1 and Th2 cell lines was also investigated. The expression of CXCR3 and CCR4 was analysed with flow cytometry. Steroid-insensitive PBMCs induced by preculture with IL-2 and IL-4 were also evaluated. Some experiments were performed in the presence of mevalonic acid.
Fluvastatin inhibited the proliferation of PBMCs and decreased the production of IL-5, IFN-gamma, CCL17, and CXCL10 after allergen-specific and non-allergen-specific stimulation; all these effects, except for decreased CXCL10 production, were partially reversed by mevalonic acid. Culture supernatants obtained in the presence of fluvastatin prevented the migration of Th1 and Th2 cell lines in a dose-dependent manner. In addition, CCR4 and CXCR3 expression on CD4(+) T cells was not affected by the presence of fluvastatin. Fluvastatin inhibited the proliferative response of steroid-insensitive PBMCs to phytohaemagglutinin.
Fluvastatin has inhibitory effects on cytokine and chemokine production, and thus might be used as a potential therapeutic agent in severe asthma.
他汀类药物对免疫细胞具有抗炎作用。
研究氟伐他汀对哮喘患者和健康受试者在变应原特异性和非变应原特异性刺激后外周血单个核细胞（PBMC）的免疫调节作用。
分离7例对屋尘螨免疫球蛋白（Ig）E升高的哮喘患者的PBMC，在有或无氟伐他汀的情况下，用粉尘螨、结核菌素纯蛋白衍生物和植物血凝素（PHA）进行刺激。用PHA刺激7名健康受试者的PBMC。测定氟伐他汀对细胞增殖、细胞因子（干扰素[IFN]-γ和白细胞介素[IL]-5）及趋化因子（CXC趋化因子基序配体[CXCL10]和CC趋化因子配体[CCL17]）产生的影响。还研究了辅助性T（Th）1和Th2细胞系的迁移。用流式细胞术分析CXCR3和CCR4的表达。对用IL-2和IL-4预培养诱导的类固醇不敏感PBMC也进行了评估。部分实验在甲羟戊酸存在的情况下进行。
氟伐他汀在变应原特异性和非变应原特异性刺激后抑制PBMC增殖，并降低IL-5、IFN-γ、CCL17和CXCL10的产生；除CXCL10产生减少外，所有这些作用均被甲羟戊酸部分逆转。在氟伐他汀存在的情况下获得的培养上清液以剂量依赖方式阻止Th1和Th2细胞系的迁移。此外，氟伐他汀的存在不影响CD4(+)T细胞上CCR4和CXCR3的表达。氟伐他汀抑制类固醇不敏感PBMC对植物血凝素的增殖反应。
氟伐他汀对细胞因子和趋化因子的产生具有抑制作用，因此可能作为重度哮喘的潜在治疗药物。
