Montelukast, Leukotriene Inhibitor, Reduces LPS-Induced Acute Lung Inflammation and Human Neutrophil Activation

Some 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.Thirty-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).Oral-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.In conclusion, montelukast efficiently attenuated both LPS-induced lung inflammation in a mouse model of ARDS and in LPS challenged human neutrophils.