Etanercept attenuates the development of cerulein-induced acute pancreatitis in mice: A comparison with TNF-α genetic deletion

Giuseppe Malleo, Emanuela Mazzon, Tiziana Genovese, Rosanna Di Paola, Carmelo Muià, Tommaso Centorrino, Ajith K. Siriwardena, Salvatore Cuzzocrea

Research output: Contribution to journalArticlepeer-review

Abstract

TNF-α plays a pivotal role in the pathogenesis of acute pancreatitis. Recent studies have shown that TNF-α inhibition significantly ameliorates the course of experimental acute pancreatitis, but in this context, the effects of Etanercept, a novel anti-TNF-α agent, have not been investigated so far. The aims of the present study are (i) to assess the effects of pharmacological inhibition of TNF-α by means of Etanercept on the inflammatory response and apoptosis in a murine model of necrotizing acute pancreatitis and (ii) to compare the results to those observed in TNF-α receptor 1 knockout (TNFR1-KO) mice. Necrotizing acute pancreatitis was induced in TNF-α wild type for TNFR1 (WT) and TNFR1-KO mice by intraperitoneal injection of cerulein (hourly ×5, 50 μg/kg). In another group of WT mice, Etanercept was administered (5 or 10 mg/kg, s.c.) at 1 h after first cerulein injection. Control groups received saline treatment. After 24 h, biochemical, histological, and immunohistochemical evidences of acute pancreatitis developed in all cerulein-treated mice; apoptosis was also present in the pancreas. Contrarily, pancreatitis histological features, amylase and lipase levels, pancreas water content, and myeloperoxidase activity were reduced in a similar degree in Etanercept-treated and TNFR1-KO mice. Likewise, in these two groups, immunohistochemical stainings and terminal deoxynucleotidyltransferase-mediated UTP nick-end labeling assay were found negative. TNF-α receptor 1 gene deletion and Etanercept administration ameliorate the course of experimental acute pancreatitis in a similar degree. Future studies on clinical applications of Etanercept in pancreatitis seem promising.

Original languageEnglish
Pages (from-to)542-551
Number of pages10
JournalShock
Volume27
Issue number5
DOIs
Publication statusPublished - May 2007

Keywords

  • Apoptosis
  • Biological therapy
  • Knockout mice
  • Neutrophils infiltration

ASJC Scopus subject areas

  • Physiology
  • Critical Care and Intensive Care Medicine

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