Effects of Tocilizumab on Experimental Severe Acute Pancreatitis and Associated Acute Lung Injury

作者：Keling Chen, Zhaoying Lv, Hongwei Yang, Yong Liu, Feiwu Long, Bin Zhou, Xiao‐Feng Sun, Zhihai Peng, Zong‐Guang Zhou, Yuan Li · 发表于：Critical Care Medicine · 年份：2016 · DOI：10.1097/ccm.0000000000001639 · 被引用次数：57 · 研究领域：Pancreatitis Pathology and Treatment、Adipokines, Inflammation, and Metabolic Diseases、Psoriasis: Treatment and Pathogenesis

OBJECTIVE: To examine the therapeutic effects of tocilizumab, an antibody against interleukin-6 receptor, on experimental severe acute pancreatitis and associated acute lung injury. The optimal dose of tocilizumab and the activation of interleukin-6 inflammatory signaling were also investigated. DESIGN: Randomized experiment. SETTING: Research laboratory at a university hospital. SUBJECT: Experimental severe acute pancreatitis in rats. INTERVENTIONS: Severe acute pancreatitis was induced by retrograde injection of sodium taurocholate (50 mg/kg) into the biliopancreatic duct. In dose-study, rats were administered with different doses of tocilizumab (1, 2, 4, 8, and 16 mg/kg) through the tail vein after severe acute pancreatitis induction. In safety-study, rats without severe acute pancreatitis induction were treated with high doses of tocilizumab (8, 16, 32, and 64 mg/kg). Serum and tissue samples of rats in time-study were collected for biomolecular and histologic evaluations at different time points (2, 6, 12, 18, and 24 hr). MEASUREMENTS AND MAIN RESULTS: 1) Under the administration of tocilizumab, histopathological scores of pancreas and lung were decreased, and severity parameters related to severe acute pancreatitis and associated lung injury, including serum amylase, C-reactive protein, lung surfactant protein level, and myeloperoxidase activity, were all significant alleviated in rat models. 2) Dose-study demonstrated that 2 mg/kg tocilizumab was the optimal treatment ...