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

Am J Respir Crit Care Med. 2000 Apr;161(4 Pt 1):1229-36. doi: 10.1164/ajrccm.161.4.9904026.


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-B(4) (LTB(4)) and LTC(4)/D(4)/E(4), 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 LTC(4)/D(4)/E(4) 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 LTB(4), 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 subset of asthmatics in whom leukotrienes are a major contributory factor in causing allergic inflammation.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Asthma / diagnosis
  • Asthma / drug therapy*
  • Asthma / immunology*
  • Bronchial Provocation Tests
  • Bronchoalveolar Lavage Fluid / chemistry
  • Bronchoalveolar Lavage Fluid / cytology
  • Cytokines / analysis
  • Double-Blind Method
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Hydroxyurea / analogs & derivatives*
  • Hydroxyurea / therapeutic use
  • Inflammation Mediators / analysis
  • Leukotriene Antagonists / therapeutic use*
  • Leukotrienes / analysis
  • Lipoxygenase Inhibitors
  • Male
  • Skin Tests


  • Cytokines
  • Inflammation Mediators
  • Leukotriene Antagonists
  • Leukotrienes
  • Lipoxygenase Inhibitors
  • zileuton
  • Hydroxyurea