• Jong Min Lee, Chang Dong Yeo, Hwa Young Lee, Chin Kook Rhee, In Kyoung Kim, Dong Gun Lee, Sang Haak Lee, and Jin Woo Kim.
• Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, School of Medicine, The Catholic University of Korea, Uijeongbu St. Mary's Hospital, 65-1 Geumo-dong, Uijeongbu, Seoul, Gyunggi-do, Republic of Korea.
• J Anesth. 2017 Jun 1; 31 (3): 397-404.

PurposePatients in whom neutropenia recovery is complicated by pneumonia have an increased risk of acute lung injury (ALI) and detrimental outcomes. The aim of the present study was to investigate whether inhibition of neutrophil elastase (NE) is effective in lipopolysaccharide (LPS)-induced ALI during neutropenia recovery in a murine model, and whether it upregulates the activation of the MerTK signaling pathway.MethodsCyclophosphamide was given to mice to induce neutropenia. Seven days later, they were administered LPS by intratracheal instillation. Sivelestat, a neutrophil elastase inhibitor, was given by intraperitoneal injection once daily starting on day 0 and continuing until mice were sacrificed on day 5 (preventive group). Alternatively, sivelestat was given after, instead of before, LPS administration on day 2 (therapeutic group).ResultsSivelestat attenuated the lung edema and histopathological changes associated with LPS-induced lung injury. The accumulation of neutrophils and the concentrations of TNF-α, IL-6, and MPO in bronchoalveolar lavage (BAL) fluids were inhibited effectively by sivelestat. The expression of ICAM-1 and NF-κB p65 was also reduced after sivelestat administration. The protein and gene expression of MerTK tended to increase with sivelestat treatment.ConclusionsSivelestat significantly attenuated LPS-induced ALI during recovery from neutropenia, and this effect was associated with MerTK induction. These findings suggest that NE inhibition could be a promising means of alleviating lung inflammation without increasing susceptibility to infection in ALI/ARDS during neutropenia recovery.

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