Anti-inflammatory effects of zileuton in a subpopulation of allergic asthmatics

The objective of this study was to determine the effects of allergen exposu re on leukotriene generation and inflammation within the airways of allergi c asthmatics and evaluate the effects of the 5-lipoxygenase inhibitor zileu ton on these responses. We measured leukotriene-B-4 (LTB4) and LTC4/D-4/E-4 inflammatory cytokine mediators, and cellular responses in bronchoalveolar lavage fluid (BALF) before and 24 h after segmental ragweed antigen challe nge in 18 asthmatic subjects at baseline. Before initiating therapy with th e 5-lipoxygenase inhibitor or placebo, only nine of 18 asthmatic subjects h ad a significant increase (234 +/- 102-fold, mean +/- SE) in BALF LTC4/D-4/ E-4 levels 24 h after segmental antigen challenge, whereas leukotriene leve ls were essentially unchanged (1.14 +/- 0.22-fold) in the other nine subjec ts. The high LT producers also had higher postantigen BALF levels of LTB4, total protein, IL-5, IL-6, TNF-alpha, and recovery of more eosinophils than the low LT producers. Treatment with the 5-lipoxygenase inhibitor zileuton reduced postantigen BALF eosinophil count by 68% in the high LT producers, but had no detectable effect on BALF composition in the low LT producers. These data suggest that leukotriene inhibition may be more effective in a s ubset of asthmatics in whom leukotrienes are a major contributory factor in causing allergic inflammation.