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) + 24 h, LPS + 24 h (10 μg/mouse), control + 48 h, LPS + 48 h, and LPS 48 h + Montelukast (10 mg/kg). In addition, human neutrophils were incubated with LPS (1 μg/mL) and treated with montelukast (10 μM).
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.
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