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Splanchnic ischemia and reperfusion injury is reduced by genetic or pharmacological inhibition of TNF‐α
Author(s) -
Esposito Emanuela,
Mazzon Emanuela,
Muià Carmelo,
Meli Rosaria,
Sessa Edoardo,
Cuzzocrea Salvatore
Publication year - 2007
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0706480
Subject(s) - superior mesenteric artery , ischemia , reperfusion injury , tumor necrosis factor alpha , medicine , myeloperoxidase , necrosis , pharmacology , inflammation , immunology , biology , pathology , endocrinology
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 wild‐type (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.