The role of tumor necrosis factor-alpha and interleukin-1 beta in ischemia-reperfusion injury of the rat small intestine

Background, To determine the role of tumor necrosis factor (TNF) and interl eukin (IL)-1 in small-intestinal ischemia-reperfusion (I-R) injury, we inve stigated the effect of FR 167653, a specific IL-I and TNF inhibitor, on war m I-R injury of the rat small intestine. Materials and methods. Male rats treated with either saline (NS group) or F R 167653 (FR group) underwent 150 min of warm small-intestinal ischemia by applying a vascular clip at the origin of the superior mesenteric artery. I n addition to the survival analyses, we investigated plasma TNF-alpha and e ndotoxin levels, intestinal tissue TNF-alpha and IL-1 beta levels, hematocr it values and the amount of exudates in the intestinal lumen, glutamic aspa rtate aminotransferase (AST), and histological findings up to 120 min after reperfusion. Results. TNF-alpha and IL-1 beta levels in the intestinal tissue, and plasm a TNF-alpha and endotoxin levels, were significantly (P < 0.05) reduced in the FR group. Severe mucosal damage on histological findings (120 min after reperfusion) and a large amount Of intraluminal exudates (60 min after rep erfusion) were shown in the NS group,but these findings were significantly (P < 0.05) ameliorated in the FR group. Serum AST levels in the NS group in creased 120 min after reperfusion, but this change was significantly (P <le ss than> 0.05) reduced in the FR group. The 30-day survival rate was 80% in the FR group and 30% in the NS group (P < 0.05). Conclusions. Dual inhibit ion of TNF and IL-1 effectively alleviated intestinal I-R injury, suggestin g the key role of TNF and IL-I in this pathophysiology. (C) 2001 Academic P ress.