Abstract |
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.
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Authors | J D Hasday, S S Meltzer, W C Moore, P Wisniewski, J R Hebel, C Lanni, L M Dubé, E R Bleecker |
Journal | American journal of respiratory and critical care medicine
(Am J Respir Crit Care Med)
Vol. 161
Issue 4 Pt 1
Pg. 1229-36
(Apr 2000)
ISSN: 1073-449X [Print] United States |
PMID | 10764316
(Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
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Chemical References |
- Cytokines
- Inflammation Mediators
- Leukotriene Antagonists
- Leukotrienes
- Lipoxygenase Inhibitors
- zileuton
- Hydroxyurea
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Topics |
- Adult
- Asthma
(diagnosis, drug therapy, immunology)
- Bronchial Provocation Tests
- Bronchoalveolar Lavage Fluid
(chemistry, cytology)
- Cytokines
(analysis)
- Double-Blind Method
- Enzyme-Linked Immunosorbent Assay
- Female
- Humans
- Hydroxyurea
(analogs & derivatives, therapeutic use)
- Inflammation Mediators
(analysis)
- Leukotriene Antagonists
(therapeutic use)
- Leukotrienes
(analysis)
- Lipoxygenase Inhibitors
- Male
- Skin Tests
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