Anti-TNF-a Therapy exerts intestinal anti-inflammatory and anti-apoptotic effects after massive bowel resection in a rat

Igor Sukhotnik, Yoav Ben-Shahar, Yulia Pollak, Shlomi Cohen, Anat Guz-Mark, Raanan Shamir

Research output: Contribution to journalArticlepeer-review

Abstract

Objectives: The aim of this study was to examine the effect of massive small bowel resection on proinflammatory cytokine intestinal expression and the effect of anti-TNF-a antibodies (ATA) on intestinal inflammation, epithelial cell turnover, and intestinal adaptation after bowel resection in rats. Methods: Male Sprague-Dawley rats were divided into 4 experimental groups: Sham-rats underwent bowel transection; Sham-ATA rats underwent bowel transection and were treated with ATA; SBS-animals underwent 75% bowel resection; and SBS-ATA rats underwent bowel resection and were treated with ATA similarly to Group B. Parameters of intestinal adaptation, enterocyte proliferation, and apoptosis were determined at sacrifice. TNF-a and apoptosis-related gene and protein levels were determined by Illumina's Digital Gene Expression (DGE) analysis, Real Time PCR, Western blotting, and immunohistochemistry. Results: From 25 genes related to TNF-a signalling that were investigated, 8 genes in the jejunum and 10 genes in the ileum were found to be up-regulated in resected versus sham animals. SBS rats demonstrated a significant increase in tissue and plasma TNF-a, IL-6 levels, intestinal mucosal TNF-a related gene expression, and microscopic parameters of inflammation. Treatment of resected animals with ATA resulted in a significant decrease in TNF-a levels, intestinal mucosal TNF-a-related gene expression, decreased number of intraepithelial lymphocytes and macrophages, and lower apoptotic index compared with SBS animals. Conclusions: In a rat model of SBS, ATA decreased plasma and tissue TNFa levels, diminished mucosal inflammation, and inhibited cell apoptosis. Anti-apoptotic effects of ATA appear to be associated with an inhibited extrinsic apoptotic pathway

Original languageEnglish
Pages (from-to)49-55
Number of pages7
JournalJournal of Pediatric Gastroenterology and Nutrition
Volume72
Issue number1
DOIs
StatePublished - Jan 2021

Keywords

  • Adaptation
  • Apoptosis
  • Intestinal inflammation
  • Proliferation
  • Short bowel syndrome
  • TNF-a

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