Anti-Leukotrienes as Novel Anti-Inflammatory Treatments in Asthma

  • Jeffrey M. Drazen
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 507)


Asthma is a chronic inflammatory disease of the airways. Among the inflammatory cells which have been implicated in the biology of asthma are eosinophils and mast cells (l-3). Although these cells have the capacity to produce a number of distinct chemical mediators, we will focus our attention exclusively on the cysteinyl leukotrienes as inflammatory mediators in asthma. We have chosen this focus, not because we believe that leukotrienes are the only mediator of importance in asthma, but rather because in the past decade a substantial body of data has accrued concerning these entities as mediators of asthma.


Peak Flow Rate Bronchoconstrictor Response Bronchoprotective Effect Chronic Stable Asthma Late Phase Airway 
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  1. 1.
    Laitinen, A. and L.A. Laitinen. 1991. Cellular infiltrates in asthma and in chronic obstructive pulmonary disease.Am Rev Respir Dis143:1159–1160.PubMedCrossRefGoogle Scholar
  2. 1.
    Bousquet, J., P. Chanez, J.Y. Lacoste, G. Barneon, N. Ghavanian, I. Enander, P. Venge, S. Ahlstedt, J. Simony-Lafontaine, and P. Godard. 1900. Eosinophilic inflammation in asthma.N.Engl.J.Med.323:1033–1039.PubMedCrossRefGoogle Scholar
  3. 1.
    Galli, S.J. 1993. New concepts about the mast cells.N.Engl.J.Med.328:257–265.PubMedCrossRefGoogle Scholar
  4. 1.
    Israel, E., E.F. Juniper, J.T. Callaghan, P.N. Mathur, M.M. Morris, A.R. Dowell, G.G. Enas, F.E. Hargreave, and J.M. Drazen. 1989. Effect of a leukotriene antagonist, LY171883, on cold air-induced bronchoconstriction in asthmatics.Am Rev Respir Dis140:1348–1353.PubMedCrossRefGoogle Scholar
  5. 1.
    Israel, E., R. Dermarkarian, M. Rosenberg, R. Sperling, G. Taylor, P. Rubin, and J.M. Drazen. 1990. The effects of a 5-lipoxygenase inhibitor on asthma induced by cold, dryair. N.Engl.J.Med.323:1740–1744.CrossRefGoogle Scholar
  6. 1.
    Manning, P.J., R.M. Watson, D.J. Margolskee, V.C. Williams, J.I. Schwartz, and P.M. O’Byrne. 1990. Inhibition of exercise-induced bronchoconstriction by MK-571, a potent leukotriene D4-receptor antagonist.N.Engl.J.Med.323:1736–1739.PubMedCrossRefGoogle Scholar
  7. 1.
    Finnerty, J.P., R. Wood-Baker, H. Thompson, and S.T. Holgate. 1992. Role of leukotrienes in exercise-induced asthma: inhibitory effect of ICI 204219, a potent LTD, receptor antagonist.Am Rev Respir Dis145:746–749.PubMedCrossRefGoogle Scholar
  8. 1.
    Makker, H.K., L.C. Lau, H.W. Thompson, S.M. Binks, and S.T. Holgate. 1993. The protective effect of inhaled leukotriene-D4receptor antagonist ICI-204,219 against exercise-induced asthma.Am Rev Respir Dis147:1413–1418.PubMedCrossRefGoogle Scholar
  9. 1.
    Adelroth, E., M.D. Inman, E. Summers, D. Pace, M. Modi, and P.M. Obyme. 1997. Prolonged protection against exercise-induced bronchoconstriction by the leukotriene D4-receptor antagonist cinalukast.J Allerg. Clin Immunol99:210–215.CrossRefGoogle Scholar
  10. 1.
    Inman, M.D., and P.M. O’Byrne. 1996. The affect of regular inhaled albuterol on exercise-induced bronchoconstriction.Am.J.Respir.Crit.CareMed. 153:65–69.CrossRefGoogle Scholar
  11. 1.
    Reiss, T.F., P. Chervinsky, R.J. Dockhorn, S. Shingo, B. Seindenberg, T.B. Edwards, and et al. 1998. Montelukast, a once daily leukotriene receptor antagonist in the treatment of chronic asthma.Arch Int Med158:1213–1220.CrossRefGoogle Scholar
  12. 1.
    Reiss, T.F., C.A. Sorkness, W. Stricker, A. Botto, W.W. Busse, S. Kundu, and J. Zhang. 1997. Effects of mntelukast (MK-0476), a potent cysteinyl leukotriene receptor antagonist, on bronchodilatation in asthmatic subjects treated with and without inhaled corticosteroids.Thorax52:45–48.PubMedCentralPubMedCrossRefGoogle Scholar
  13. 1.
    Dahlen, S.E., B. Dahlen, E. Elliason, H. Johansson, T. Bjorck, M. Kumlin, K. Boo, J. Whitney, S. Binks,B. King, and et al. 1991. Inhibition of allergic bronchoconstriction in asthmatics by the leokotrieneantagonist ICI-204,219.Adv.Prost.Thromb.Leukot.Res21A:461–464.Google Scholar
  14. 1.
    Taylor, I.K., K.M. O’Shaughnessy, R.W. Fuller, and C.T. Dollery. 1991. Effect of cysteinyl-leukotriene receptor antagonist ICI-204,219 on allergen-induced bronchoconstriction and airway hyperreactivity in atopic subjects.Lancet337:690–694.PubMedCrossRefGoogle Scholar
  15. 1.
    Findlay, S.R., J.M. Barden, C.B. Easley, and M. Glass. 1992. Effect of the oral leukotriene anatagonist, ICI-204,219 on antigen-induced bronchoconstriction in subjects with asthma.J. Allergy Clin. Immunol.89:1040–1045.PubMedCrossRefGoogle Scholar
  16. 1.
    Rasmussen, J.B., D.J. Margolskee, L.O. Eriksson, V.C. Williams, and K.E. Anderson. 1991. Leukotriene (LT) D4 is involved in antigen-induced asthma: a study with the LTD4receptor antagonist, MK-571.Ann. N. Y Acad. Sci.629:436–436.PubMedCrossRefGoogle Scholar
  17. 1.
    Gaddy, J.N., D.J. Margolskee, R.K. Bush, V.C. Williams, and W.W. Busse. 1992. Bronchodilation with a potent and selective leukotriene D4 (LTD4) antagonist (MK-571) in patients with asthma.Am Rev Respir Dis146:358–363.PubMedCrossRefGoogle Scholar
  18. 1.
    Impens, N., T.F. Reiss, J.A. Teahan, M. Desmet, T.H. Rossing, S. Shingo, Z. Ji, W. Schandevyl, R. Verbesselt, and A.G. Dupont. 1993. Acute bronchodilation with an intravenously administered leukotriene-D(4) antagonist, MK-679.Am Rev Respir Dis147:1442–1446.PubMedCrossRefGoogle Scholar
  19. 1.
    Oshaughnessy, K.M., I.K. Taylor, B. Oconnor, F. Oconnell, H. Thompson, and C.T. Dollery. 1993. Potent leukotriene-D(4) receptor antagonist ICI-204,219 given by the inhaled route inhibits the early but not the late phase of allergen-induced bronchoconstriction.Am Rev Respir Dis147:1431–1435.CrossRefGoogle Scholar
  20. 1.
    Friedman, B.S., E.H. Bel, A. Buntinx, W. Tanaka, Y.H.R. Han, S. Shingo, R. Spector, and P. Sterk. 1993. Oral leukotriene inhibitor (MK-886) blocks allergen-induced airway responses.Am Rev Respir Dis147:839–844.PubMedCrossRefGoogle Scholar
  21. 1.
    Roquet, A., B. Dahlen, M. Kumlin, E. Ihre, G. Anstren, S. Binks, and S.E. Dahlen. 1997. Combined antagonism of leukotrienes and histamine produces predominant inhibition of allergen-induced early and late phase airway obstruction in asthmatics.Amer.J.Respir.Crit.Care Med.155:1856–1863.CrossRefGoogle Scholar
  22. 1.
    Cloud, M.L., G.C. Enas, J. Kemp, T. Platts-Mills, L.C. Altman, R. Townley, D. Tinkelman, T. King, Jr., E. Middleton, A.L. Sheffer, and et al. 1989. A specific LTD4/LTE4-receptor antagonist improves pulmonary function in patients with mild, chronic asthma. AmRev Respir Dis140:1336–1339.PubMedCrossRefGoogle Scholar
  23. 1.
    Israel, E., P. Rubin, J.P. Kemp, J. Grossman, W.E. Pierson, S.C. Siegel, D. Tinkelman, J.J. Murray, W. Busse, A.T. Segal, J. Fish, H.B. Kaiser, D. Ledford, S. Wenzel, R. Rosenthal, J. Cohn, C. Lanni, H. Pearlman, P. Karahalios, and J.M. Drazen. 1993. The effect of inhibition of 5-lipoxygenase by zileuton in mild to moderate asthma.Ann.Intern.Med.119:1059–1066.PubMedCrossRefGoogle Scholar
  24. 1.
    Spector, S.L., L.J. Smith, M. Glass, B.K. Birmigham, E.A. Bronsky, K.D. Dunn, J.E. Fish, J. Grossman, W. Howland, M.C. Minkwitz, J.S. Larsen, R.A. Nathan, S.I. Rennard, E.S. Schulman, A. segal, and L.M. Seltzer. 1994. Effects of 6 weeks of therapy with oral doses of ICI-204,219 a leukotriene D4 receptor antagonist, in subjects with bronchial asthma.Am.J.Respir.Crit.Care Med150:618–623.PubMedCrossRefGoogle Scholar
  25. 1.
    Barnes, N.C., and J.C. Pujet. 1997. Pranlukast, a novel leukotriene receptor antagonist: results of the first european, placebo controlled, multicenter clinical study in asthma.Thorax52:523–527.PubMedCentralPubMedCrossRefGoogle Scholar
  26. 1.
    Drazen, J.M., E. Israel, and P.M. Obyrne. 1999. Treatment of asthma with drugs modifying the leukotriene pathway.N.Engl.J.Med.340:197–206.PubMedCrossRefGoogle Scholar
  27. 1.
    Reiss, T.F., P. Chervinsky, R.J. Dockhorn, S. Shingo, B. Seindenberg, and T.B. Edwards. 1998. Montelukast, a once-daily leukotriene receptor antagonist, in the treatment of chronic asthma: a multicenter, randomized, double-blind trial. Montelukast Clinical Research Study Group.Arch.lntern. Med.158:1213–1220.CrossRefGoogle Scholar
  28. 1.
    Fish, J.E., J.P. Kemp, R.F. Lockey, M. Glass, L.A. Hanby, and C.M. Bonuccelli. 1997. Zafirlukast for symptomatic mild to moderate asthma: a 13-week multicenter study. The Zafirlukast Trialists Group.Clin.Ther.19:675–690.PubMedCrossRefGoogle Scholar
  29. 1.
    Israel, E., J. Cohn, L. Dube, and J.M. Drazen. 1996. Effect of treatment with zileuton, a 5-lipoxygenase inhibitor, in patients with asthma: a randomized controlled trial.JAMA275:931–936.PubMedCrossRefGoogle Scholar
  30. 1.
    Liu, M.C., L.M. Dube, and J. Lancaster. 1996. Acute and chronic effects of a 5-lipoxygenase inhibitor in asthma: a 6-month randomized multicenter trial. Zileuton Study Group.J Allergy Clin. Immunol98:859–871.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • Jeffrey M. Drazen
    • 1
  1. 1.Combined Program in Pulmonary and Critical Care Medicine, Department of MedicineBrigham and Women’s Hospital and Harvard Medical SchoolBostonMA

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