Role of interleukin 18 in acute lung inflammation induced by gut ischemia reperfusion

AIM： To study the changes of endogenous interleukin 18 （IL-18） levels and evaluate the role of IL-18 on lung injury following gut ischemia/reperfusion. METHODS： A superior mesenteric artery occlusion model was selected for this research. The mice were randomly divided into four groups： Sham operation （sham）, ischemia （0.5 h） followed by different times of reperfusion （I/R）, and I/R pretreated with exogenous IL-18 （I/R＋IL-18） or IL-18 neutralizing antibody （I/R＋IL-18Ab） 15 min before ischemia. Serum IL-18 levels were detected by Western blot and ELISA, and the levels of IL-18 in lung tissue were evaluated by immunohistochemical staining. For the study of pulmonary inflammation, the lung myeloperoxidase （MPO） contents and morphological changes were evaluated. RESULTS： Gut ischemia/reperfusion induced rapid increase of serum IL-18 levels, peaked at 1 h after reperfusion and then declined. The levels of IL-18 in lung tissue were gradually enhanced as the progress of reperfusion. Compared with I/R group, exogenous administration of IL-18 （I/R＋IL-18） further remarkably enhanced the pulmonary MPO activity and inflammatory cell infiltration, and in I/R＋IL-18Ab group, the content of MPO were significantly reduced and lung inflammation was also decreased. CONCLUSION： Gut ischemia/reperfusion induces the increase of IL-18 expression, which may make IL-18 act as an important proinflammatory cytokine and contribute to gut ischemia/reperfusion-induced lung inflammation.