Role of tumour necrosis factor in lung injury caused by intestinal ischaemia-reperfusion

Background: Despite the well known inflammatory effects of tumour necrosis factor alpha (TNF), the mechanism of TNF-mediated lung injury following isc haemia-reperfusion (I/R) is still unclear. In this study, the role of TNF i n the development of acute lung injury following intestinal I/R was investi gated. Methods: Male Wistar rats underwent either sham operation (n = 10), 1 h of superior mesenteric artery occlusion and 2 h of reperfusion (I/R, n = 10), or pretreatment with anti-TNF polyclonal antibody 2 mg/ kg and I/R (n = 6). Lung injury was evaluated by Evans blue dye concentration, immunohistochem ical staining and morphometric analysis. Intestinal injury was assessed by Evans blue dye concentration and histological examination. Results: Intestinal I/R resulted in lung injury characterized by an increas e in Evans blue dye concentration, neutrophil sequestration, and obvious st aining for expression of pulmonary CD11b and CD18. Pretreatment of animals with anti-TNF antibody led to a reduction in the sequestration of neutrophi ls, and a decrease in expression of pulmonary intracellular adhesion molecu le 1 and CD18. Anti-TNF antibody pretreatment also reduced the intestinal m icrovascular injury but not histological grade after intestinal I/R. Conclusion: Treatment with an anti-TNF antibody resulted in a significant a ttenuation of lung injury following intestinal I/R. The data indicate that TNF is an important trigger for upregulation of pulmonary endothelial and n eutrophil adhesion molecules after intestinal I/R.