Gonçalves Isabel, Cherfan Pierre, Söderberg Ingrid, Nordin Fredrikson Gunilla, Jonasson Lena
Department of Cardiology, Malmo University Hospital, Sweden.
Autoimmunity. 2009 Mar;42(3):203-8. doi: 10.1080/08916930802668602.
Statins exert a number of anti-inflammatory and immunomodulatory effects in vitro. However, the immunomodulatory effects in vivo are less clarified. In the present study, we investigated whether simvastatin treatment changed the levels of autoantibodies against specific oxidized LDL (oxLDL) antigens as well as their association with leukocyte activation markers. Eighty volunteers with mild-to-moderate hypercholesterolemia were randomized to either simvastatin 40 mg or placebo for 6 weeks. Autoantibodies against apo B peptide antigens, C-reactive protein (CRP) and interleukin (IL)-6 in plasma were determined by ELISA. Subsets of circulating B and T cells were studied by flow cytometry. Simvastatin significantly reduced CRP by 26%, whereas IL-6 remained unchanged. Levels of IgG against the apo B peptide P-240 (amino acids 3586-3605) increased by 16% (p = 0.03) in the simvastatin group whereas autoantibody levels to other apo B peptides did not change. At baseline and after 6 weeks, the P-240 IgG levels were significantly correlated with the number of CD57+CD28 - CD8+T cells but not to other lymphocyte subsets or inflammatory markers. The P-240 IgG levels after 6 weeks simvastatin therapy was strongly correlated to the relative increase in CD57+CD28 - CD8+T cells (p = 0.003). Simvastatin treatment induced an increase in autoantibodies against an oxLDL antigen. The effect was related to an expansion of a CD8+T cell subset and may involve an immunostimulation by simvastatin.
他汀类药物在体外具有多种抗炎和免疫调节作用。然而，其体内的免疫调节作用尚不清楚。在本研究中，我们调查了辛伐他汀治疗是否会改变针对特定氧化低密度脂蛋白（oxLDL）抗原的自身抗体水平及其与白细胞活化标志物的关联。80名轻至中度高胆固醇血症志愿者被随机分为辛伐他汀40mg组或安慰剂组，治疗6周。采用酶联免疫吸附测定法（ELISA）测定血浆中针对载脂蛋白B肽抗原、C反应蛋白（CRP）和白细胞介素（IL）-6的自身抗体。通过流式细胞术研究循环B细胞和T细胞亚群。辛伐他汀使CRP显著降低26%，而IL-6保持不变。辛伐他汀组中，针对载脂蛋白B肽P-240（氨基酸3586 - 3605）的IgG水平升高了16%（p = 0.03），而针对其他载脂蛋白B肽的自身抗体水平未改变。在基线和6周后，P-240 IgG水平与CD57 + CD28 - CD8 + T细胞数量显著相关，但与其他淋巴细胞亚群或炎症标志物无关。辛伐他汀治疗6周后的P-240 IgG水平与CD57 + CD28 - CD8 + T细胞的相对增加密切相关（p = 0.003）。辛伐他汀治疗导致针对oxLDL抗原的自身抗体增加。这种效应与一个CD8 + T细胞亚群的扩增有关，可能涉及辛伐他汀的免疫刺激作用。
