Kempf K, Haltern G, Füth R, Herder C, Müller-Scholze S, Gülker H, Martin S
German Diabetes Clinic, German Diabetes Center, Leibniz Institute at the Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.
Horm Metab Res. 2006 May;38(5):346-51. doi: 10.1055/s-2006-925403.
Inflammation contributes to the development of atherosclerosis and cardiovascular events. Counteracting pro- and anti-inflammatory responses of serum cytokines have been reported, but the relevance of TNF-alpha, TGF-beta and IL-6 gene expression in peripheral blood leukocytes and their contribution to systemic inflammation in atherosclerosis, especially after acute myocardial infarction (AMI), has not been investigated yet. Using quantitative RT-PCR, we determined temporal cytokine mRNA expression alterations in blood cells from patients with AMI (n = 51). Serum cytokine concentrations were analyzed in parallel using the ELISA technique. TNF-alpha mRNA expression rates and serum concentrations were significantly elevated in AMI patients compared to controls (n = 77), while mRNA expression and serum content of TGF-beta were decreased. Interestingly, we found no statistically significant correlation between transcript and protein levels, indicating that gene expression in leukocytes may be an independent sign for systemic inflammation. While IL-6 was significantly increased in serum from AMI patients with positive correlation to left ventricular dysfunction and negative correlation to ejection fraction, IL-6 mRNA levels did not differ between patients and controls. Gene expression alterations indicate a sophisticated regulation of counteracting TNF-alpha and TGF-beta cytokine expression in peripheral blood leukocytes after AMI with bias towards a pro-inflammatory situation.
炎症促进动脉粥样硬化的发展和心血管事件的发生。已有报道血清细胞因子的促炎和抗炎反应相互抵消，但外周血白细胞中肿瘤坏死因子-α（TNF-α）、转化生长因子-β（TGF-β）和白细胞介素-6（IL-6）基因表达的相关性及其在动脉粥样硬化（尤其是急性心肌梗死（AMI）后）全身炎症中的作用尚未得到研究。我们采用定量逆转录聚合酶链反应（RT-PCR）技术，测定了51例AMI患者血细胞中细胞因子mRNA表达的时间变化。同时采用酶联免疫吸附测定（ELISA）技术分析血清细胞因子浓度。与77例对照组相比，AMI患者的TNF-α mRNA表达率和血清浓度显著升高，而TGF-β的mRNA表达和血清含量降低。有趣的是，我们发现转录水平和蛋白水平之间无统计学显著相关性，这表明白细胞中的基因表达可能是全身炎症的一个独立指标。虽然AMI患者血清中的IL-6显著升高，与左心室功能障碍呈正相关，与射血分数呈负相关，但患者与对照组之间的IL-6 mRNA水平无差异。基因表达变化表明，AMI后外周血白细胞中TNF-α和TGF-β细胞因子表达的抵消调节较为复杂，且倾向于促炎状态。
