Leukotriene A4 Hydrolase Inhibition Attenuates Allergic Airway Inflammation and Hyperresponsiveness

Rationale: Allergic asthma is characterized by reversible airway obstruction, lung inflammation, and airway hyperresponsiveness (AHR). Previous studies using leukotriene B4 (LTB4) receptor 1–deficient mice and adoptive transfer experiments have suggested that LTB4 plays a role in lung inflammation and AHR.Objectives: In this study, we used a leukotriene A4 hydrolase (LTA4H) inhibitor as a pharmacological tool to directly examine the role of LTB4 in a mast cell–dependent murine model of allergic airway inflammation.Methods: We used the forced oscillation technique to test the effects of an LTA4H inhibitor dosed during the challenge phase on AHR. Lung tissue and lavage were collected for analysis.Measurements and Main Results: Treatment with an LTA4H inhibitor improved multiple parameters encompassing AHR and lung function. Significant decreases in inflammatory leukocytes, cytokines, and mucin were observed in the lung lumen. Serum levels of antigen-specific IgE and IgG1 were also decreased. Labeled antigen...