Slide Session : OS-113 ; Lung Cancer : Neutrophil Elastase Inhibition Contributes to Attenuation of Lipopolysaccharide-Induced Acute Lung Injury During Neutropenia Recovery in Mice = Slide Session : OS-113 ; Lung Cancer : Neutrophil Elastase Inhibition Contributes to Attenuation of Lipopolysaccharide-Induced Acute Lung Injury During Neutropenia Recovery in Mice

다국어 초록 (Multilingual Abstract)

Background: A high proportion of patients in whom neutropenia had been complicated by pneumonia during neutropenia recovery are related to an increased risk of acute lung injury (ALI) and detrimental outcomes. The aim of the present study is to investigate whether neutrophil elastase (NE) inhibition is effective in murine LPS-induced ALI during neutropenia recovery and whether NE inhibition suppresses the activation of Mer signaling pathway. Methods: Cyclophosphamide was given to mice to induce neutropenia. Mice were administrated by intratracheal instillation of LPS seven days after cyclophosphamide administration. Sivelestat, neutrophuil elastase inhibitor, was given by intraperitoneal injection once daily starting on day 0 and continuing until mice were sacrificed on day 5 (preventive group). In addition, sivelestat was given after, instead of before, LPS administration on day 2 (therapeutic group). Results: Sivelestat attenuated the lung edema and histopathological change of LPS-induced lung injury. The accumulation of neutrophils and the concentrations of TNF-a, IL-6 and MPO in BAL fiuids were effectively inhibited by sivelestat. The gene expression of Mer tyrosine kinase was increased by sivelestat treatment. Conclusions: Sivelestat significantly attenuated LPS induced ALI during neutropenia recovery. These findings suggest NE inhibition could be a promising target alleviating lung infiammation without increasing susceptibility to infection in ALI/ARDS during neutropenia recovery.