Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia (UdeA), Calle 70 No. 52-21, Medellín, Colombia.
Epiontis GmbH, 12489 Berlin, Germany.
J Immunol Res. 2015;2015:762506. doi: 10.1155/2015/762506. Epub 2015 Feb 22.
Statins have been shown to modulate the number and the suppressive function of CD4(+)FOXP3(+) T cells (Treg) in inflammatory conditions. However, it is not well established whether statin could also affect Treg in absence of inflammation. To address this question, eighteen normocholesterolemic male subjects were treated with lovastatin or atorvastatin daily for 45 days. The frequency and phenotype of circulating Treg were evaluated at days 0, 7, 30, and 45. mRNA levels of FOXP3, IDO, TGF-β, and IL-10 were measured in CD4(+) T cells. We found that both statins significantly increased Treg frequency and FOXP3 mRNA levels at day 30. At day 45, Treg numbers returned to baseline values; however, TGF-β and FOXP3 mRNA levels remained high, accompanied by increased percentages of CTLA-4- and GITR-expressing Treg. Treg Ki-67 expression was decreased upon statin treatment. Treg frequency positively correlated with plasma levels of high-density lipoprotein cholesterol (HDL-c), suggesting a role for HDL-c in Treg homeostasis. Therefore, statins appear to have inflammation-independent immune-modulatory effects. Thus, the increase in Treg cells frequency likely contributes to immunomodulatory effect of statins, even in healthy individuals.
他汀类药物已被证明可调节炎症状态下 CD4(+)FOXP3(+)T 细胞（Treg）的数量和抑制功能。然而，他汀类药物是否也能在没有炎症的情况下影响 Treg 尚不清楚。为了解决这个问题，18 名正常胆固醇血症的男性受试者每天接受洛伐他汀或阿托伐他汀治疗 45 天。在第 0、7、30 和 45 天评估循环 Treg 的频率和表型。在 CD4(+)T 细胞中测量 FOXP3、IDO、TGF-β 和 IL-10 的 mRNA 水平。我们发现两种他汀类药物在第 30 天均显著增加 Treg 频率和 FOXP3 mRNA 水平。在第 45 天，Treg 数量恢复到基线值；然而，TGF-β 和 FOXP3 mRNA 水平仍然很高，同时伴有 CTLA-4 和 GITR 表达的 Treg 百分比增加。他汀类药物治疗后 Treg 的 Ki-67 表达减少。Treg 频率与高密度脂蛋白胆固醇（HDL-c）的血浆水平呈正相关，提示 HDL-c 在 Treg 稳态中起作用。因此，他汀类药物似乎具有非炎症免疫调节作用。因此，Treg 细胞频率的增加可能有助于他汀类药物的免疫调节作用，即使在健康个体中也是如此。
