TY - JOUR T1 - Montelukast, Leukotriene Inhibitor, Reduces LPS-Induced Acute Lung Inflammation and Human Neutrophil Activation JO - Archivos de Bronconeumología T2 - AU - Davino-Chiovatto,Jaime Eduardo AU - Oliveira-Junior,Manoel Carneiro AU - MacKenzie,BreAnne AU - Santos-Dias,Alana AU - Almeida-Oliveira,Ana Roberta AU - Aquino-Junior,Jefferson Comin Jonco AU - Brito,Auriléia Aparecida AU - Rigonato-Oliveira,Nicole Cristine AU - Damaceno-Rodrigues,Nilsa Regina AU - Oliveira,Ana Paula Ligeiro AU - Silva,Alessandro Pereira AU - Consolim-Colombo,Fernanda Marciano AU - Aimbire,Flavio AU - Castro-Faria-Neto,Hugo Caire AU - Vieira,Rodolfo Paula SN - 03002896 M3 - 10.1016/j.arbres.2019.05.003 DO - 10.1016/j.arbres.2019.05.003 UR - https://archbronconeumol.org/en-montelukast-leukotriene-inhibitor-reduces-lps-induced-articulo-S0300289619302558 AB - ObjectivesSome pro-inflammatory lipids derived from 1 lipooxygenase enzyme are potent neutrophil chemoattractant, a cell centrally involved in acute respiratory distress syndrome (ARDS); a syndrome lacking effective treatment. Considering the beneficial effects of the leukotriene receptor inhibitor, montelukast, on other lung diseases, whether montelukast attenuates inflammation in a mouse model of ARDS, and whether it reduces LPS stimulated activation of human neutrophils was investigated. MethodsThirty-five C57Bl/6 mice were distributed into control (PBS)+24h, LPS+24h (10μg/mouse), control+48h, LPS+48h, and LPS 48h+Montelukast (10mg/kg). In addition, human neutrophils were incubated with LPS (1μg/mL) and treated with montelukast (10μM). ResultsOral-tracheal administration of montelukast significantly attenuated total cells (P<.05), macrophages (P<.05), neutrophils (P<.01), lymphocytes (P<.001) and total protein levels in BAL (P<.05), as well as IL-6 (P<.05), CXCL1/KC (P<.05), IL-17 (P<.05) and TNF-α (P<.05). Furthermore, montelukast reduced neutrophils (P<.001), lymphocytes (P<.01) and macrophages (P<.01) in the lung parenchyma. In addition, montelukast restored BAL VEGF levels (P<.05). LTB4 receptor expression (P<.001) as well as NF-κB (P<.001), a downstream target of LPS, were also reduced in lung parenchymal leukocytes. Furthermore, montelukast reduced IL-8 (P<.001) production by LPS-treated human neutrophils. ConclusionIn conclusion, montelukast efficiently attenuated both LPS-induced lung inflammation in a mouse model of ARDS and in LPS challenged human neutrophils. ER -