Interleukin-1으로 유도된 흰쥐 급성폐손상에서 neutrophil elastase 억제제인 ICI 200,355의 효과
Effect of Neutrophil Elastase inhibitor, ICI 200,355, on Interleukin-1 Induced acute lung injury in rats
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Background: Interleukin-1 (IL-1) and neutrophil appear to contribute to the pathogenesis of acute respiratory distress syndrome (ARDS). Elastase, as well as reactive oxygen species released from activated neutrophil, are thought to play pivotal roles in the experimental models of acute lung leak. This study investigated whether ICI 200,355, a synthetic elastase inhibitor, can attenuate acute lung injury induced by IL-1 in rats. Materials and Methods: We intratracheally instilled either saline or IL-1 with and without treatment of ICI 200,355 in rats. Lung lavage neutrophils, lung lavage cytokine-induced neutrophil chemoattractant(CINC) concentration, lung lavage protein concentration, lung myeloperoxidase(MPO) activity and lung leak index were measured at 5 hours of intratracheal treatment. Results: In rats given IL-1 intratracheally, lung lavage neutrophils, lung lavage CINC concentration, lung lavage protein concentration, lung MPO activity and lung leak index were higher. Intratracheal ICI 200,355 administration decreased lung lavage neutrophils, lung MPO activity and lung leak index, respectively, but did not decreased lung lavage CINC concentration. Conclusion: These results suggest that ICI 200,355 decreases lung inflammation and leak without decreasing lung lavage CINC concentration in rats given IL-1 intratracheally.
Abstract
Background: Interleukin-1 (IL-1) and neutrophil appear to contribute to the pathogenesis of acute respiratory distress syndrome (ARDS). Elastase, as well as reactive oxygen species released from activated neutrophil, are thought to play pivotal roles in the experimental models of acute lung leak. This study investigated whether ICI 200,355, a synthetic elastase inhibitor, can attenuate acute lung injury induced by IL-1 in rats. Materials and Methods: We intratracheally instilled either saline or IL-1 with and without treatment of ICI 200,355 in rats. Lung lavage neutrophils, lung lavage cytokine-induced neutrophil chemoattractant(CINC) concentration, lung lavage protein concentration, lung myeloperoxidase(MPO) activity and lung leak index were measured at 5 hours of intratracheal treatment. Results: In rats given IL-1 intratracheally, lung lavage neutrophils, lung lavage CINC concentration, lung lavage protein concentration, lung MPO activity and lung leak index were higher. Intratracheal ICI 200,355 administration decreased lung lavage neutrophils, lung MPO activity and lung leak index, respectively, but did not decreased lung lavage CINC concentration. Conclusion: These results suggest that ICI 200,355 decreases lung inflammation and leak without decreasing lung lavage CINC concentration in rats given IL-1 intratracheally.