Anti-inflammatory Effects of Zileuton in a Subpopulation of Allergic Asthmatics

The objective of this study was to determine the effects of allergen exposure on leukotriene generation and inflammation within the airways of allergic asthmatics and evaluate the effects of the 5-lipoxygenase inhibitor zileuton on these responses. We measured leukotriene-B4 (LTB4) and LTC4/D4/E4, inflammatory cytokine mediators, and cellular responses in bronchoalveolar lavage fluid (BALF) before and 24 h after segmental ragweed antigen challenge in 18 asthmatic subjects at baseline. Before initiating therapy with the 5-lipoxygenase inhibitor or placebo, only nine of 18 asthmatic subjects had a significant increase (234 ± 102-fold, mean ± SE) in BALF LTC4/D4/E4 levels 24 h after segmental antigen challenge, whereas leukotriene levels were essentially unchanged (1.14 ± 0.22-fold) in the other nine subjects. The high LT producers also had higher postantigen BALF levels of LTB4, total protein, IL-5, IL-6, TNF- α , and recovery of more eosinophils than the low LT producers. Treatment with the 5-lipoxygenase ...