Okopień Boguslaw, Krysiak Robert, Kowalski Jan, Madej Andrzej, Belowski Dariusz, Zieliński Marek, Labuzek Krzysztof, Herman Zbigniew S
Department of Clinical Pharmacology, Medical University of Silesia, Medyków 18, PL 40-752 Katowice, Poland.
Atherosclerosis. 2004 Oct;176(2):327-35. doi: 10.1016/j.atherosclerosis.2004.05.009.
The aim of the study was to assess the effect of two major groups of hypolipemic drugs, HMG-CoA reductase inhibitors (statins) and PPARalpha activators (fibrates), on the secretory function of T-lymphocytes in patients with primary type II dyslipidemia. Sixty-three patients with type IIa dyslipidemia were randomized to fluvastatin (40 mg daily; n = 33) or simvastatin (20mg daily; n = 30), while 68 type IIb dyslipidemic patients were treated with micronized ciprofibrate (100mg daily; n = 34) or micronized fenofibrate (200mg daily; n = 34). Lipid profile and cytokine (interferon-gamma and interleukin-2) release by phytohemagglutinin-stimulated lymphocytes were determined at the beginning of the study and after 30 and 90 days of treatment. Compared to healthy subjects (n = 59), both type IIa and IIb dyslipidemic patients exhibited higher baseline release of interferon-gamma and interleukin-2. Fluvastatin, simvastatin and, to a less extent, ciprofibrate and fenofibrate inhibited the release of both cytokines, but this effect did not correlate with their lipid-lowering potential. Hypolipemic agents also slightly reduced plasma interleukin-2 levels. Our study suggests that the beneficial effect of hypolipemic drugs involves their inhibitory action on the secretory function of T-lymphocytes. This lipid-independent action is stronger for statins than for fibrates and probably results from their "class" effect. The treatment-induced reduction in the release of both cytokines may contribute to the clinical effectiveness of statins and fibrates in the therapy of atherosclerosis and in the management of organ transplant recipients.
本研究的目的是评估两类主要的降血脂药物，即HMG-CoA还原酶抑制剂（他汀类药物）和PPARα激活剂（贝特类药物）对原发性II型血脂异常患者T淋巴细胞分泌功能的影响。63例IIa型血脂异常患者被随机分为氟伐他汀组（每日40mg；n = 33）或辛伐他汀组（每日20mg；n = 30），而68例IIb型血脂异常患者接受微粒化环丙贝特（每日100mg；n = 34）或微粒化非诺贝特（每日200mg；n = 34）治疗。在研究开始时以及治疗30天和90天后，测定血脂谱以及植物血凝素刺激的淋巴细胞释放的细胞因子（干扰素-γ和白细胞介素-2）。与健康受试者（n = 59）相比，IIa型和IIb型血脂异常患者的干扰素-γ和白细胞介素-2基线释放均较高。氟伐他汀、辛伐他汀以及在较小程度上的环丙贝特和非诺贝特均抑制了这两种细胞因子的释放，但这种作用与其降脂潜力无关。降血脂药物还略微降低了血浆白细胞介素-2水平。我们的研究表明，降血脂药物的有益作用涉及其对T淋巴细胞分泌功能的抑制作用。这种不依赖脂质的作用他汀类药物比贝特类药物更强，可能是由于它们的“类效应”。治疗引起的两种细胞因子释放减少可能有助于他汀类药物和贝特类药物在动脉粥样硬化治疗以及器官移植受者管理中的临床疗效。
