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

• DOI: 10.1189/jlb.0706480
• Publication Date: 2007-01-09T01:14:07Z
• Authors: Emanuela Esposito; Emanuela Mazzon; Carmelo Muià; Rosaria Meli; Edoardo Sessa; Salvatore Cuzzocrea
• Keywords: Male; Mice, Knockout; 0301 basic medicine; Fas Ligand Protein; Recombinant Fusion Proteins; Apoptosis; Immunohistochemistry; Receptors, Tumor Necrosis Factor; Etanercept; 3. Good health; Intestines; Mice; 03 medical and health sciences; Neutrophil Infiltration; Proto-Oncogene Proteins c-bcl-2; Ischemia; Immunoglobulin G; Reperfusion Injury; Animals; Lipid Peroxidation; Splanchnic Circulation; Cell Adhesion Molecules; Immunosuppressive Agents

In the present study, we used TNF-alpha receptor 1 knockout (TNF-alphaR1KO) mice to evaluate a possible role of on pathogenesis ischemia and reperfusion injury multivisceral organs. Ischemia was induced in by clamping superior mesenteric artery celiac for 30 min, followed thereafter reperfusion. Sixty minutes after reperfusion, animals were killed histological examination biochemical studies. Injured wild-type (WT) developed significant increase ileum levels, myeloperoxidase activity, marked apoptosis. organs also associated with mortality. Reperfused sections from injured WT showed positive staining P-selectin, VCAM, ICAM-1, E-selectin. The intensity degree E-selectin, ICAM-1 reduced markedly tissue TNF-alphaR1KO mice. reperfusion-injured reduction neutrophil infiltration into intestine, apoptosis, an improved status survival. addition, investigated effect Etanercept, soluble construct, Etanercept (5 mg/kg administered i.p. 5 min prior reperfusion) significantly inflammatory response injury. Taken together, our results clearly demonstrate that plays important put forward hypothesis modulation expression may represent novel strategy.