Xiao Liu1, Xiaorong Guo, Jie Li, Min Wu, Xianbao Zhan. 1. From the Departments of *Gastroenterology and †Oncology, Changhai Hospital, Second Military Medical University, Shanghai, China.
Abstract
OBJECTIVES: It has been confirmed that the initiation of acute pancreatitis (AP) involves intracellular trypsinogen activation and local cytokines release during its early stage. The former is related to autophagic disorder, and the latter is resulting from nuclear factor-κB activation. Although great efforts have been exerted, there is still nonspecific treatment currently. Recent data showed that immunomodulatory therapy is always promising. However, the effects of interferon-γ (IFN-γ) on AP are controversial. This study is designed to elucidate the effects of IFN-γ on AP severity and explore its impacts on the major mechanisms of AP. METHODS: Sprague-Dawley rats were used to establish AP model by intraperitoneal injection of 20% L-arginine (4 g/kg) twice with an interval of 1 hour. The effects of IFN-γ on the severity of AP, trypsinogen activation peptide, and tumor necrosis factor α, Interleukin-1, Interleukin-6 levels, and autophagy activity were detected. RESULTS: Compared with AP rats without IFN-γ administration, AP rats with IFN-γ administration had more severe pathological changes in pancreata, greater levels of trypsinogen activation concomitant with autophagy up-regulation, and higher levels of cytokine release. CONCLUSIONS: Interferon-γ aggravated L-arginine-induced AP in Sprague-Dawley rats and led to intracellular trypsinogen activation and inflammatory response. The former may be related to autophagy up-regulation.
OBJECTIVES: It has been confirmed that the initiation of acute pancreatitis (AP) involves intracellular trypsinogen activation and local cytokines release during its early stage. The former is related to autophagic disorder, and the latter is resulting from nuclear factor-κB activation. Although great efforts have been exerted, there is still nonspecific treatment currently. Recent data showed that immunomodulatory therapy is always promising. However, the effects of interferon-γ (IFN-γ) on AP are controversial. This study is designed to elucidate the effects of IFN-γ on AP severity and explore its impacts on the major mechanisms of AP. METHODS:Sprague-Dawley rats were used to establish AP model by intraperitoneal injection of 20% L-arginine (4 g/kg) twice with an interval of 1 hour. The effects of IFN-γ on the severity of AP, trypsinogen activation peptide, and tumor necrosis factor α, Interleukin-1, Interleukin-6 levels, and autophagy activity were detected. RESULTS: Compared with AP rats without IFN-γ administration, AP rats with IFN-γ administration had more severe pathological changes in pancreata, greater levels of trypsinogen activation concomitant with autophagy up-regulation, and higher levels of cytokine release. CONCLUSIONS: Interferon-γ aggravated L-arginine-induced AP in Sprague-Dawley rats and led to intracellular trypsinogen activation and inflammatory response. The former may be related to autophagy up-regulation.
Authors: Pranav Murthy; Aatur D Singhi; Mark A Ross; Patricia Loughran; Pedram Paragomi; Georgios I Papachristou; David C Whitcomb; Amer H Zureikat; Michael T Lotze; Herbert J Zeh Iii; Brian A Boone Journal: Front Immunol Date: 2019-01-24 Impact factor: 7.561