Statin Modulation of Human T-Cell Proliferation, IL-1β and IL-17 Production, and IFN-γ T Cell Expression: Synergy with Conventional Immunosuppressive Agents.
Statin Modulation of Human T-Cell Proliferation, IL-1β and IL-17 Production, and IFN-γ T Cell Expression: Synergy with Conventional Immunosuppressive Agents.
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DOI：
10.1155/2013/434586
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发表时间：
2013
影响因子：
2
通讯作者：
Calder VL
中科院分区：
文献类型：
--
作者：
Jameel A;Ooi KG;Jeffs NR;Galatowicz G;Lightman SL;Calder VL
HMG-CoA还原酶抑制剂（他汀类药物）已被证明对人类免疫介导的疾病和实验模型具有免疫调节作用。本研究的目的是比较他汀类药物介导的体外免疫抑制对人t细胞反应的影响与传统免疫抑制剂（地塞米松、环孢素A （CsA）、霉酚酸盐和雷帕霉素）的影响。研究了他汀类药物（阿托伐他汀、洛伐他汀和辛伐他汀）对人PBMC活力、细胞因子谱和t细胞增殖的调节作用。在抑制抗cd3 /28刺激的t细胞增殖（P < 0.01）的浓度下，辛伐他汀显著降低细胞内CD4+ t细胞中IFN-γ的表达（P < 0.01），与常规免疫抑制剂诱导的水平相似。阿托伐他汀和洛伐他汀也能降低IFN-γ的表达，但程度较轻（P < 0.05）。三种他汀类药物均可降低IL-17的生成水平（P < 0.01）。然而，在抗cd3 /28刺激下，辛伐他汀显著上调IL-1β的产生（P < 0.05）。与单独使用地塞米松相比，添加阿托伐他汀和地塞米松时，抗cd3 /28刺激产生的细胞因子谱相似，这表明阿托伐他汀可以与地塞米松协同调节细胞因子。这一数据支持了选择性他汀介导的免疫调节作用对人类免疫细胞的假设。
HMG-CoA reductase inhibitors (statins) have been demonstrated to be immunomodulatory for human immune-mediated disease and in experimental models. The aim of this study was to compare statin-mediated immunosuppressive effects on human T-cell responses in vitro with those of conventional immunosuppressives (dexamethasone, cyclosporin A (CsA), mycophenolate, and rapamycin). Statins (atorvastatin, lovastatin, and simvastatin) were investigated for their modulatory effects on human PBMC viability, cytokine profiles, and T-cell proliferation. At concentrations that inhibited anti-CD3/28-stimulated T-cell proliferation (P < 0.01), simvastatin significantly decreased intracellular CD4+ T-cell expression of IFN-γ (P < 0.01) to levels similar to those induced by conventional immunosuppressives. Atorvastatin and lovastatin also decreased IFN-γ expression, although to a lesser degree (P < 0.05). All three statins reduced levels of IL-17 production (P < 0.01). However, in response to anti-CD3/28 stimulation, simvastatin significantly upregulated IL-1β production (P < 0.05). The profile of cytokines produced in response to anti-CD3/28 stimulation was similar when both atorvastatin and dexamethasone were added as compared with dexamethasone alone, suggesting that atorvastatin can synergise with dexamethasone with respect to immunomodulation of cytokines. This data supports the hypothesis of selective statin-mediated immunomodulatory effects on human immune cells.