Effect of montelukast on nuclear factor κB activation and proinflammatory molecules

Background: Montelukast is known as a cysteinyl leukotriene I receptor antagonist. However, the action of montelukast in terms of nuclear factor kappa B (NF-kappa B). activation and the production of proinflammatory molecules is unknown. Objective: To demonstrate the potential anti-inflammatory effect of montelukast. Methods: We examined whether montelukast inhibits the activation of NF-kappa B, a transcription factor that regulates the expression of proinflammatory molecules. The inhibitory effects of montelukast on tumor necrosis factor alpha (TNF-alpha)-induced NF-kappa B activation on THP-1 cells, a human monocytic leukemia cell line, were evaluated by flow cytometry, and those on lipopolysaccharide-induced interleukin 1 beta (IL-1 beta), IL-6, TNF-alpha, and monocyte chemoattractant protein 1 (MCP-1) production in peripheral blood mononuclear cells were evaluated by enzyme-linked immunosorbent assay. Results: Flow cytometry demonstrated that montelukast inhibited NF-kappa B activation in THP-1 cells in a dose-related manner. Furthermore, 10-M-5 montelukast significantly inhibited lipopolysaccharide-induced IL-6, TNF-alpha, and MCP-1 production in the peripheral blood mononuclear cells of controls and patients with asthma. Lipopolysaccharide-induced IL-1 beta production was not inhibited by montelukast. Conclusions: These findings suggest that high doses of montelukast modulate the production of IL-6, TNF-alpha, and MCP-1 through the inhibition of NF-kappa B activation. However, the anti-inflammatory effect of montelukast at therapeutic doses in patients with asthma needs to be further investigated.