Abstract
We have previously demonstrated that Doxofylline (Dox) at 1 and 0.3 mg/kg significantly inhibited leukocyte migration and cytokine release in a murine model of lung inflammation induced by lipopolysaccharide (LPS) (Riffo-Vasquez et. al., Pulm. Pharm. Ther. 2014, Epub.) Montelukast (Mltk) is a leukotriene receptor antagonist used in the treatment of allergic lung diseases, often alongside xanthines. In this study we have investigated the effect of the combination of Dox and Mltk in a model of lung inflammation induced by LPS. Methods: Dox (0.3 mg/kg i.p.) and Mltk (0.3 mg/kg, oral or 1 mg/kg i.p.) were administrated -24, -1 and 6 h after LPS (10 µg/mice, i.n.) in Balb/c mice. The combination of the drugs did not induce any adverse effects. Lung lavage was performed 24 h later. Results: LPS recruited significantly higher number of neutrophils (PMN) to the lung (mean±SEM x 106/ml) compared to saline (saline:0±0 vs LPS:1.8±0.15, n=6). Dox alone significantly inhibited the recruitment of PMN (LPS/Dox:1.02±0.1, n =5; p<0.05 vs LPS). Mltk alone by oral administration or i.p. had no significant effect on the number of PMN (LPS/Mtlk oral:1.99±0.19, LPS/Mtlk i.p.:1.64±0.31, n=5 and 4, respectively). The combination of Dox and Mltk did not provide any further significantly effect on the number of PMN recruited to the lung in response to LPS (LPS/Dox±Mtlk oral.:2.34±0.34, LPS/Dox±Mtlk i.p.:1.9±0.2, n=5 and 4, respectively). Conclusion: Doxofylline is an effective anti-inflammatory drug, a property not shared by montelukast in this model. Therefore, combination treatment of doxofylline and montelukast gives additional benefits compared to montelukast as mono therapy.
- © 2014 ERS
