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 ischaemia-reperfusion (I/R) is still unclear. In this study, the role of TNF in the development of acute lung injury following intestinal I/R was investigated.


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, immunohistochemical 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 increase in Evans blue dye concentration, neutrophil sequestration, and obvious staining for expression of pulmonary CD11b and CD18. Pretreatment of animals with anti-TNF antibody led to a reduction in the sequestration of neutrophils, and a decrease in expression of pulmonary intracellular adhesion molecule 1 and CD18. Anti-TNF antibody pretreatment also reduced the intestinal microvascular injury but not histological grade after intestinal I/R.


CONCLUSIONS
Treatment with an anti-TNF antibody resulted in a significant attenuation of lung injury following intestinal I/R. The data indicate that TNF is an important trigger for upregulation of pulmonary endothelial and neutrophil adhesion molecules after intestinal I/R.
Department of Surgery, Ankara University Medical School, Ankara, Turkey.
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C
Köksoy
M A
MA
Kuzu
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I
Kuzu
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H
Ergün
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I
Gürhan
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D018821:CD18 Antigens / Q000378:metabolism; D003250:Constriction; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007422:Intestines / Q000098:blood supply*; D007511:Ischemia / Q000150:complications*; D008168:Lung / Q000098:blood supply; D008171:Lung Diseases / Q000209:etiology*; D016177:Macrophage-1 Antigen / Q000378:metabolism; D008297:Male; D017538:Mesenteric Artery, Superior / Q000601:surgery; D008833:Microcirculation; D051381:Rats; D015427:Reperfusion Injury / Q000150:complications*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000502:physiology*; D015854:Up-Regulation
D000906:Antibodies; D018821:CD18 Antigens; D016177:Macrophage-1 Antigen; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1