Pulmonary cachexia, systemic inflammatory profile, and the interleukin 1β-511 single nucleotide polymorphism
Pulmonary cachexia, systemic inflammatory profile, and the interleukin 1β-511 single nucleotide polymorphism
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DOI：
10.1093/ajcn/82.5.1059
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发表时间：
2005-11-01
影响因子：
7.1
通讯作者：
Schols, AM
中科院分区：
文献类型：
--
作者：
Broekhuizen, R;Grimble, RF;Schols, AM
背景资料：恶病质在慢性阻塞性肺疾病（COPD）中很常见，并且被认为与增强的全身炎症反应有关。目的：我们研究COPD患者全身炎症特征和相关炎症基因多态性的差异。设计：对99例COPD患者进行了横断面研究（慢性阻塞性肺疾病全球倡议II-IV期），根据无脂肪质量指数，（FFMI;单位kg/m2：男性< 16，女性< 15），并与健康对照受试者（HC）进行比较。通过生物电阻抗分析确定身体组成。测定白细胞介素1 β（IL-1 β-511）、IL-6（IL-6 -174）和肿瘤坏死因子系统（TNF-α-308和TNF-α +252）的血浆浓度和基因多态性。结果：非恶病质患者（NCPs）和恶病质患者（CPs：n = 35）之间的脂肪量、瘦素和假尿苷有显著差异（P < 0.001）;全身炎性细胞因子无显著差异（P> 0.05）。与HC相比，NCP的身体成分向较低的无脂肪质量和较高的脂肪质量转变。CP和NCP的全身炎症反应比HC更强（P < 0.05），这反映在C反应蛋白、可溶性TNF-R75和IL-6浓度上。IL-1 β-511多态性的总体分布在各组之间有显著性差异（P < 0.05）。结论：COPD患者以全身炎症反应升高为特征，恶病质与炎症状态的增加程度无关。然而，这项研究表明，恶病质过程中的遗传易感性的潜在影响。
Background: Cachexia is common in chronic obstructive pulmonary disease (COPD) and is thought to be linked to an enhanced systemic inflammatory response.Objective: We investigated differences in the systemic inflammatory profile and polymorphisms in related inflammatory genes in COPD patients.Design: A cross-sectional study was performed in 99 patients with COPD (Global Initiative for Chronic Obstructive Lung Disease stages II-IV), who were stratified by cachexia based on fat-free mass index (FFMI; in kg/m(2): < 16 for men and < 15 for women) and compared with healthy control subjects (HCs). Body composition was determined by bioelectrical impedance analysis. Plasma concentrations and gene polymorphisms of interleukin 1 beta (IL-1 beta -511), IL-6 (IL-6 -174), and the tumor necrosis factor system (TNF-alpha -308 and lymphotoxin-alpha +252) were determined. Plasma C-reactive protein, leptin, and urinary pseudouridine (as a marker of cellular protein breakdown) were measured.Results: Fat mass, leptin, and pseudouridine were significantly different (P < 0.001) between noncachectic patients (NCPs) and cachectic patients (CPs: n = 35); the systemic inflammatory cytokine profile was not. NCPs had a body compositional shift toward a lower fat-free mass and a higher fat mass compared with HCs. CPs and NCPs had a greater systemic inflammatory response (P < 0.05) than did HCs, as reflected in C-reactive protein, soluble TNF-R75, and IL-6 concentrations. The overall distribution of the IL-1 beta -511 polymorphism was significantly different between the groups (P < 0.05).Conclusions: In COPD patients, who are characterized by an elevated systemic inflammatory response, cachexia is not discriminatory for the extent of increase in inflammatory status. This study, however, indicates a potential influence of genetic predisposition on the cachexia process.