Casadevall Carme, Coronell Carlos, Ausín Pilar, Martínez-Llorens Juana, Orozco-Levi Mauricio, Barreiro Esther, Gea Joaquim
Servei de Pneumologia-URMAR, Hospital del Mar-Institut Municipal d'Investigació Mèdica (IMIM), Universitat Pompeu Fabra (UPF), Barcelona, España.
Arch Bronconeumol. 2009 Jun;45(6):279-85. doi: 10.1016/j.arbres.2008.11.009. Epub 2009 Apr 29.
There is disagreement regarding the local action of cytokines in the respiratory muscles of patients with chronic obstructive pulmonary disease (COPD). The objective of this study was to analyze the relationships between cytokine expression and genetic activation of the mechanisms of muscle repair.
Twenty-five patients with severe COPD and in stable condition were enrolled in the study. We performed a biopsy of the external intercostal muscle of the patients and analyzed the specimen for signs of muscle lesion (morphometry), infiltration of inflammatory cells (immunohistochemistry), and expression of selected genes (real-time polymerase chain reaction technique) corresponding to the cytokines (tumor necrosis factor alpha [TNF-alpha] and its type 1 and 2 receptors [TNFR1 and TNFR2], and interleukin [IL] 1beta, IL-6, and IL-10), a pan-leukocyte marker (CD18), and key molecules in the repair-myogenesis pathways (Pax7, M-cadherin, and MyoD).
Expression of TNFR2 is directly related to inspiratory muscle function (represented by maximum sustainable inspiratory pressure; r=0.496; P<.05), whereas expression of CD18 is inversely related (r=0.462; P<.05). Moreover, expression of the 2 TNF-alpha receptors was directly related to that of the key molecules of the repair pathways analyzed (TNFR1 to Pax7 [r=0.650; P<.001] and M-cadherin [r=0.678; P<.001]; TNFR2 to Pax7 [r=0.395; P<.05], M-cadherin [r=0.409; P<.05], and MyoD [r=0.418; P<.05]).
Expression of TNF-alpha receptors bears a close relationship both to activation of the myogenesis programs and to inspiratory muscle function. This reinforces our hypothesis that some local cytokines take part in the repair of respiratory muscles in patients with COPD.
关于细胞因子在慢性阻塞性肺疾病（COPD）患者呼吸肌中的局部作用存在分歧。本研究的目的是分析细胞因子表达与肌肉修复机制的基因激活之间的关系。
本研究纳入了25例病情稳定的重度COPD患者。我们对患者的肋间外肌进行活检，并分析标本的肌肉损伤迹象（形态学测量）、炎性细胞浸润（免疫组织化学）以及对应细胞因子（肿瘤坏死因子α [TNF-α]及其1型和2型受体[TNFR1和TNFR2]、白细胞介素[IL] 1β、IL-6和IL-10）、全白细胞标志物（CD18）以及修复-成肌途径中的关键分子（Pax7、M-钙黏蛋白和MyoD）的选定基因的表达（实时聚合酶链反应技术）。
TNFR2的表达与吸气肌功能直接相关（以最大可持续吸气压力表示；r = 0.496；P <.05），而CD18的表达则呈负相关（r = 0.462；P <.05）。此外，两种TNF-α受体的表达与所分析的修复途径关键分子的表达直接相关（TNFR1与Pax7 [r = 0.650；P <.001]和M-钙黏蛋白[r = 0.678；P <.001]；TNFR2与Pax7 [r = 0.395；P <.05]、M-钙黏蛋白[r = 0.409；P <.05]和MyoD [r = 0.418；P <.05]）。
TNF-α受体的表达与成肌程序的激活以及吸气肌功能密切相关。这强化了我们的假设，即某些局部细胞因子参与了COPD患者呼吸肌的修复。
