Urinary trypsin inhibitor attenuates seawater-induced acute lung injury by influencing the activities of nuclear factor-κB and its related inflammatory mediators

Abstract

Background: Few data are available on the role of neutrophil elastase (NE) and nuclear factor-κB (NF-κB) in the course of seawater drowning-induced acute lung injury (SWD-ALI), and there is no evidence on the value of giving urinary trypsin inhibitor (UTI) in the case of SWD-ALI. Objective: To investigate the role of NF-κB and NE in the pathogenesis of SWD-ALI and whether UTI treatment can attenuate SWD-ALI in rabbits. Methods: Rabbits were randomly assigned to control, seawater drowning, and UTI treatment groups. The rabbits in the control group only suffered from intubation, whereas the rabbits in the seawater drowning group and the UTI treatment group received arterial injection of normal saline without/with 50,000 U/kg body weight of UTI after instillation of seawater into an endotracheal catheter. The activities or contents of NF-κB, MPO, NE, TNF-α, and IL-10 in lung tissue were measured by nonradioactive EMSA, biochemical methods, and ELISA, respectively. Results: After the seawater challenge, all of the rabbits demonstrated immediate drops in arterial PaO 2/FiO 2 and pronounced pulmonary edema and inflammatory cell infiltration with evidence of an increase in the ratio of wet weight to dry weight, lung permeability index, lung injury scores, and the activities or contents of NF-κB, NE, MPO, TNF-α, and IL-10. UTI treatment markedly attenuated lung histopathological changes with evidence of a decrease in all of the parameters, except for upregulation of IL-10. Arterial PaO 2/FiO 2 was significantly improved after 6 h of UTI treatment. Conclusion: These results suggest that NF-κB and NE play an important role in SWD-ALI. UTI protects against SWD-ALI, at least partly, through inhibition of the enhanced local activity of NF-κB, contents of TNF-α and NE, and infiltration of neutrophils and promotion of the level of IL-10. Copyright © 2011 S. Karger AG.