Role of tumour necrosis factor in lung injury caused by intestinal ischaemia–perfusion

Abstract

Abstract Background Despite the well known inflammatory effects of tumour necrosis factor (TNF), the mechanism of TNF-mediated lung injury following ischaemia–reperfusion (IR) is still unclear. In this study, the role of TNF in the development of acute lung injury following intestinal IR was investigated. Methods Male Wistar rats underwent either sham operation (n = 10) or 1 h of superior mesenteric artery occlusion and 2 h of reperfusion (IR; n = 10) or pretreatment with anti-TNF polyclonal antibody 2 mg kg−1 and IR (n = 6). Lung injury was evaluated by Evans blue dye concentration, immunohistochemical staining and morphometric analysis. Intestinal injury was assessed by Evans blue dye concentration and histological examination. Results Intestinal IR resulted in lung injury characterized by an increase in Evans blue dye concentration, polymorphonuclear neutrophil (PMN) sequestration, and obvious staining for expression of pulmonary CD11b and CD18. Pretreatment of animals with anti-TNF antibodies led to a reduction in the sequestration of PMNs (P < 0·05), a decrease in expression of pulmonary intercellular adhesion molecule 1 and CD18 (P < 0·01), and a diminished histological grade compared with the IR-only group. Anti-TNF antibody pretreatment also reduced the intestinal microvascular injury after intestinal IR. Conclusion Treatment with an anti-TNF antibody resulted in significant attenuation of lung injury following intestinal IR, which is at least partially TNF mediated. The data indicate that TNF is an important trigger for upregulation of pulmonary endothelial and neutrophil adhesion molecules after intestinal IR.