Rhinovirus Infection Increases 5‐Lipoxygenase and Cyclooxygenase‐2 in Bronchial Biopsy Specimens from Nonatopic Subjects

Abstract

Rhinovirus infections cause wheeze, cough, and bronchial hyperresponsiveness. To investigate the involvement of cysteinyl-leukotrienes and prostanoids in these symptoms, bronchial biopsy specimens from 9 normal subjects (nonatopic and with no history of chronic lung disease) were immunostained for 5-lipoxygenase (5-LO) and cyclooxygenase (COX) pathway enzymes 2 weeks before and 4 days after experimental infection with human rhinovirus serotype 16.5-LO-positive cell counts increased 9-fold (from 0.48 to 4.4 cells/mm²; P <.05), and 5- LO-activating protein (FLAP)-positive cell counts increased 3.6-fold (from 1.8 to 6.5 cells/ mm²; P = .09). Levels of leukotriene A₄ hydrolase and leukotriene C₄ synthase were unchanged. COX-2-positive cell counts increased from 0 to 2.6 cells/mm² (P = .009), with no change in COX-1 levels. Increases of 3-4-fold were seen in levels of macrophages (P = .02) and mast cells (P = .07) but not of eosinophils (P > .4), and bronchoalveolar lavage fluid cysteinyl-leukotriene levels doubled (from 11.2 to 20.4 pg/mL; P = .13). Cold symptom scores correlated with bronchial immunostaining for FLAP (ρ = 0.93; P = .001). In normal subjects, rhinovirus colds induce bronchial inflammation with markedly enhanced expression of 5-LO pathway proteins and COX-2.