Splanchnic ischemia and reperfusion injury is reduced by genetic or pharmacological inhibition of TNF-α

Emanuela Esposito, Emanuela Mazzon, Carmelo Muià, Rosaria Meli, Edoardo Sessa, Salvatore Cuzzocrea

Research output: Contribution to journalArticle

Abstract

In the present study, we used TNF-α receptor 1 knockout (TNF-αR1KO) mice to evaluate a possible role of TNF-α on the pathogenesis of ischemia and reperfusion injury of the multivisceral organs. Ischemia and reperfusion injury was induced in mice by clamping the superior mesenteric artery and the celiac artery for 30 min, followed thereafter by reperfusion. Sixty minutes after reperfusion, animals were killed for histological examination and biochemical studies. Injured wildtype (WT) mice developed a significant increase of ileum TNF-α levels, myeloperoxidase activity, and marked histological injury and apoptosis. Ischemia and reperfusion injury of the multivisceral organs was also associated with a significant mortality. Reperfused ileum sections from injured WT mice showed positive staining for P-selectin, VCAM, ICAM-1, and E-selectin. The intensity and degree of P-selectin, E-selectin, VCAM, and ICAM-1 were reduced markedly in tissue sections from injured TNF-αR1KO mice. Ischemia and reperfusion-injured TNF-αR1KO mice also showed a significant reduction of neutrophil infiltration into the intestine, a reduction of apoptosis, an improved histological status of the intestine, and survival. In addition, we investigated the effect of Etanercept, a TNF-α soluble receptor construct, on ischemia and reperfusion injury of the multivisceral organs. Etanercept (5 mg/kg administered i.p. 5 min prior to reperfusion) significantly reduced the inflammatory response and the ileum injury. Taken together, our results clearly demonstrate that TNF-α plays an important role in the ischemia and reperfusion injury and put forward the hypothesis that modulation of TNF-α expression may represent a novel and possible strategy.

Original languageEnglish
Pages (from-to)1032-1043
Number of pages12
JournalJournal of Leukocyte Biology
Volume81
Issue number4
DOIs
Publication statusPublished - Apr 2007

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Keywords

  • Adhesion molecules
  • Etanercept
  • Neutrophil infiltration

ASJC Scopus subject areas

  • Cell Biology

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