ABSTRACT
Objectives To explore ventilation induced cytokine production and the role of oxidant stress in lung stretch. Methods Both in vitro and in vivo models of ventilator-induced lung injury (VILI) were used. Alveolar epithelial cells were stretched in vitro to mimic the lung injury in VILI. Rats were ventilated at large tidal volume to produce ventilator-induced lung injury in vivo. A total of 23 inflammatory cytokines were screened with micro gene array in stretched alveolar epithelial cells. Cytokines found to have up-regulated in cells were measured in serum and lung tissue of rats exposed to large tidal volume ventilation. For investigating the intracellular pathway of cytokine up-regulation in VILI, exogenous TNF-? or H_ 2O_ 2 was added to culture media of alveolar epithelial cells. Cytokines were then measured. To explore the role of oxidant stress in VILI, N-acetylcysteine (NAC), as an anti-oxidant, was used in vitro and in vivo. Results We found that transforming growth factor-?_1 (TGF-?_1 and transforming growth factor-?_2 (TGF-?_2) were up-regulated in stretched alveolar epithelial cells and also in serum of rats with large tidal volume ventilation. Tumor necrosis factor-? (TNF-?) had no effects on TGF-? production in alveolar epithelial cells. Exogenous H_ 2O_ 2, as an oxidant, increased TGF-? production in alveolar epithelial cells. NAC, an anti-oxidant, decreased stretch induced TGF-? production, along with a down-regulation of oxidant injury. NAC also blocked the up-regulation of TGF-? in in vivo model of VILI. Conclusion TGF-?_1 and TGF-?_2 were up-regulated in VILI. Oxidant injury mediated up-regulation of TGF-? in VILI. NAC, which attenuated oxidant injury and blocked TGF-? up-regulation in VILI, could be a future therapeutic strategy in VILI.