Department of Emergency and Intensive Care Unit, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
J Clin Immunol. 2013 Oct;33(7):1257-68. doi: 10.1007/s10875-013-9923-0. Epub 2013 Jul 11.
Cytokines play a critical role in the development of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Here we investigated whether IL-27 was elevated in patients with ALI/ARDS and its potential clinical significance. Bronchoalveolar lavage (BAL) and serum samples were obtained from 58 ALI/ARDS patients, and 25 control healthy volunteers. IL-27 and other inflammatory mediators were measured in BAL and serum by ELISA. Besides, a mouse model of cecal ligation and puncture (CLP)-induced lung inflammation/injury was established, and serum, BAL fluid and tissues were collected for analyses in the presence or absence of IL-27 neutralizing antibodies. BAL IL-27 was found to be significantly higher in patients with ALI/ARDS than that in controls, particularly of pulmonary origin; serum IL-27 was also significantly higher. Increased IL-27 was associated with markers of inflammation, and correlated with disease severity of patients in ALI/ARDS. In a mouse model of CLP-induced lung inflammation/injury, elevated IL-27 levels were observed in the lung, serum, and BAL fluids. IL-27 neutralizing antibody treatment reduced pulmonary inflammation and lung injury and improved mouse survival in response to CLP. Therefore, IL-27 is a critical cytokine in ALI/ARDS and inhibition of IL-27 may open a promising approach for ALI/ARDS patients.
细胞因子在急性肺损伤(ALI)/急性呼吸窘迫综合征(ARDS)的发展中起着关键作用。在这里,我们研究了 IL-27 是否在 ALI/ARDS 患者中升高及其潜在的临床意义。收集了 58 例 ALI/ARDS 患者和 25 例对照健康志愿者的支气管肺泡灌洗液(BAL)和血清样本。通过 ELISA 测量 BAL 和血清中的 IL-27 和其他炎症介质。此外,建立了盲肠结扎和穿刺(CLP)诱导的肺部炎症/损伤的小鼠模型,并在存在或不存在 IL-27 中和抗体的情况下收集血清、BAL 液和组织进行分析。发现 ALI/ARDS 患者的 BAL 中 IL-27 明显高于对照组,特别是肺来源的 IL-27;血清 IL-27 也明显升高。增加的 IL-27 与炎症标志物相关,并且与 ALI/ARDS 患者的疾病严重程度相关。在 CLP 诱导的肺部炎症/损伤的小鼠模型中,肺部、血清和 BAL 液中观察到 IL-27 水平升高。IL-27 中和抗体治疗可减轻肺部炎症和肺损伤,并提高 CLP 后小鼠的存活率。因此,IL-27 是 ALI/ARDS 的关键细胞因子,抑制 IL-27 可能为 ALI/ARDS 患者提供一种有前途的治疗方法。