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

Arch Bronconeumol (Engl Ed). 2019 Nov;55(11):573-580. doi: 10.1016/j.arbres.2019.05.003. Epub 2019 Jun 27.
[Article in English, Spanish]

Abstract

Objectives: 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.

Methods: 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).

Results: 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.

Conclusion: In conclusion, montelukast efficiently attenuated both LPS-induced lung inflammation in a mouse model of ARDS and in LPS challenged human neutrophils.

Keywords: Acute lung injury; Citoquinas; Cytokines; Daño pulmonar agudo; Factores de crecimiento; Growth factors; Inflamación; Inflammation; Leucotrieno; Leukotriene; Neutrophils; Neutrófilos.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetates / pharmacology*
  • Animals
  • Bronchoalveolar Lavage
  • Capillary Permeability / drug effects
  • Cyclopropanes
  • Cytokines / analysis
  • Cytokines / drug effects
  • Humans
  • Leukocyte Count
  • Leukotriene Antagonists / pharmacology*
  • Lipopolysaccharides
  • Lung / cytology
  • Lymphocytes / drug effects
  • Macrophages / drug effects
  • Mice
  • Mice, Inbred C57BL
  • NF-kappa B / drug effects
  • NF-kappa B / metabolism
  • Neutrophil Activation / drug effects*
  • Neutrophils / drug effects
  • Neutrophils / metabolism
  • Pneumonia / chemically induced
  • Pneumonia / prevention & control*
  • Quinolines / pharmacology*
  • Receptors, Leukotriene B4 / drug effects
  • Receptors, Leukotriene B4 / metabolism
  • Respiratory Distress Syndrome / chemically induced
  • Respiratory Distress Syndrome / etiology
  • Sulfides
  • Time Factors
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Acetates
  • Cyclopropanes
  • Cytokines
  • Leukotriene Antagonists
  • Lipopolysaccharides
  • NF-kappa B
  • Quinolines
  • Receptors, Leukotriene B4
  • Sulfides
  • Vascular Endothelial Growth Factor A
  • vascular endothelial growth factor A, mouse
  • montelukast