• Ke-Ling Chen, Zhao-Ying Lv, Hong-Wei Yang, Yong Liu, Fei-Wu Long, Bin Zhou, Xiao-Feng Sun, Zhi-Hai Peng, Zong-Guang Zhou, and Yuan Li.
• 1Institute of Digestive Surgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China. 2Department of Gastroenterological Surgery, West China Hospital, Sichuan University, Chengdu, China. 3Department of Oncology, Department of Clinical and Experiment Medicine, Linköping University, Linköping, Sweden. 4Department of General Surgery, Shanghai First People's Hospital, Shanghai Jiaotong University, Shanghai, China.
• Crit. Care Med. 2016 Aug 1; 44 (8): e664-77.

ObjectiveTo 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.DesignRandomized experiment.SettingResearch laboratory at a university hospital.SubjectExperimental severe acute pancreatitis in rats.InterventionsSevere 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 Results1) 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 dose. 3) Basing on multi-organ pathologic evaluation, physiological and biochemical data, no adverse effect and toxicity of tocilizumab were observed in safety-study. 4) Pancreatic nuclear factor-κB and signal transducer and activator of transcription 3 were deactivated, and the serum chemokine (C-X-C motif) ligand 1 was down-regulated after tocilizumab administration.ConclusionsOur study demonstrated tocilizumab, as a marketed drug commonly used for immune-mediated diseases, was safe and effective for the treatment of experimental severe acute pancreatitis and associated acute lung injury. Our findings provide experimental evidences for potential clinical application of tocilizumab in severe acute pancreatitis and associated complications.

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