Skip to main content

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 525))

Abstract

One of the major reasons for pursuing the chemical structure of the biological material known as slow-reacting substance of anaphylaxis (SRS-A) was that this material was known to be a potent bronchoconstrictor substance in guinea pigs [1] and in isolated human airways [2]. Thirty years ago, the simple concept was that SRS-A was released from sensitized cells following antigen sensitization and challenge, and that the released material transduced a signal at an as yet to be identified receptor leading to smooth muscle constriction and therefore the manifestations of human asthmA. It has been almost 25 years since the elucidation of the structure of SRS-A as a mixture of the cysteinyl leukotrienes (LT) [3] and just over 5 years since agents that act on leukotriene pathway have been available as asthma treatments [4,5]. What have we learned about asthma from the use of these agents and what is the role of these agents in the treatment of asthma?

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Drazen JM, Austen KF. Effects of intravenous administration of slow-reacting substance of anaphylaxis, histamine, bradykinin, and prostaglandin F2alpha on pulmonary mechanics in the guinea piG. J Clin Invest 1974; 53:1679–1685.

    Article  PubMed  CAS  Google Scholar 

  2. Brocklehurst WE. The release of histamine and the formation of a slow-reacting substance (SRS-A) during anaphylactic shock. J Physiol (Lond) 1960; 151:416–435.

    CAS  Google Scholar 

  3. Murphy RC, Hammarstrom S, Samuelsson B. Leukotriene C: a slow-reacting substance from murine mastocytoma cells. Proc Natl Acad Sci USA 1979; 76:4275–4279.

    Article  PubMed  CAS  Google Scholar 

  4. Obyrne PM, Israel E, Drazen JM. Antileukotrienes in the treatment of asthma. Ann Intern Med 1997; 127(6):472–480.

    CAS  Google Scholar 

  5. Drazen JM, Israel E, Obyrne PM. Treatment of asthma with drugs modifying the leukotriene pathway. N Engl J Med 1999; 340(3):197–206.

    Article  PubMed  CAS  Google Scholar 

  6. Lewis RA, Austen KF, Soberman RJ. Leukotrienes and other products of the 5-lipoxygenase pathway. Biochemistry and relation to pathobiology in human diseases. N Engl J Med 1990; 323:645–655.

    Article  PubMed  CAS  Google Scholar 

  7. Dahlen SE, Hedqvist P, Hammarstrom S, Samuelsson B. Leukotrienes are potent constrictors of human bronchi. Nature 1980; 288:484–486.

    Article  PubMed  CAS  Google Scholar 

  8. Weiss JW, Drazen JM, Coles N, McFadden ERJ, Weller PF, Corey EJ et al. Bronchoconstrictor effects of leukotriene C in humans. Science 1982; 216:196–198.

    Article  PubMed  CAS  Google Scholar 

  9. Hammarstrom S, Orning L, Bernstrom K. Metabolism and excretion of cysteinyl-leukotrienes. Adv Prost Thromb Leukot Res 1986; 16:383–396.

    CAS  Google Scholar 

  10. Taylor GW, Taylor I, Black P, Maltby NH, Turner N, Fuller RW et al. Urinary leukotriene E4 after antigen challenge and in acute asthma and allergic rhinitis. Lancet 1989; 1:584–588.

    Article  PubMed  CAS  Google Scholar 

  11. Drazen JM, Obrien J, Sparrow D, Weiss ST, Martins MA, Israel E et al. Recovery of Leukotriene-E4 from the Urine of Patients with Airway Obstruction. Am Rev Respir Dis 1992; 146:104–108.

    PubMed  CAS  Google Scholar 

  12. Asano K, Lilly CM, Odonnell WJ, Israel E, Fischer A, Ransil BJ et al. Diurnal variation of urinary leukotriene E4 and histamine excretion rates in normal subjects and patients with mild-to-moderate asthmA. J Allergy Clin Immunol 1995; 96(5 Part 1):643–651.

    CAS  Google Scholar 

  13. Hui KP, Barnes NC. Lung function improvement in asthma with a cysteinyl-leukotriene receptor antagonist. Lancet 1991; 337:1062–1063.

    Article  PubMed  CAS  Google Scholar 

  14. Israel E, Rubin P, Kemp JP, Grossman J, Pierson WE, Siegel SC et al. The effect of inhibition of 5-lipoxygenase by zileuton in mild to moderate asthma. Ann Intern Med 1993; 119:1059–1066.

    PubMed  CAS  Google Scholar 

  15. Malmstrom K, Rodriguez-Gomez G, Guerra J, Villaran C, Pineiro A, Wei LX et al. Oral montelukast, inhaled beclomethasone, and placebo for chronic asthma. A randomized controlled trial. Ann Int Med 1999; 130:487–495.

    PubMed  CAS  Google Scholar 

  16. Drazen JM, Silverman EK, Lee TH. Heterogeneity of therapeutic responses in asthma. Brit Med Bull 2000; 56(4):1054–1070.

    Article  PubMed  CAS  Google Scholar 

  17. Awni WM, Locke C, Dube LM, Cavanaugh JH. Evaluation of the diurnal variation in the pharmacokinetics of zileuton in healthy volunteers. J Clin Pharmacol 1997; 37(5):388–394.

    PubMed  CAS  Google Scholar 

  18. Drazen JM, Yandava C, Dube L, Szczerback N, Hippensteel R, Pillari A et al. Pharmacogenetic association between ALOX5 promoter genotype and the response to anti-asthma treatment. Nature Genetics 1999; 22:170–172.

    Article  Google Scholar 

  19. Asano K, Shiomi T, Hasegawa N, Nakamura H, Kudo H, Matsuzaki T et al. Leukotriene C4 synthase gene A(-444)C polymorphism and clinical response to a CYS-LT1 antagonist, in Japanese patients with moderate asthma. Pharmacogenetics 2002; 12:1–6.

    Google Scholar 

  20. Bleecker ER, Welch MJ, Weinstein SF, Kalberg C, Johnson M, Edwards L et al. Low-dose inhaled fluticasone propionate versus oral zafirlukast in the treatment of persistent asthma. J Allergy Clin Immunol 2000 Jun; 105(6 Pt 1):1123–9 2000; 105(6 Pt 1):1123-1129.

    Article  PubMed  CAS  Google Scholar 

  21. Laviolette M, Malmstrom K, Lu S, Chervinsky P, Pujet JC, Peszek I et al. Montelukast added to inhaled beclomethasone in treatment of asthma. Amer J Respir Crit Care Med 1999; 160(6):1862–1868.

    CAS  Google Scholar 

  22. Yokoyama A, Kohno N, Sakai K, Hirasawa Y, Kondo K, Hiwada K. Effect of pranlukast, a leukotriene receptor antagonist, in patients with severe asthma refractory to corticosteroids. J Asthma 1998; 35(1):57–62.

    Article  PubMed  CAS  Google Scholar 

  23. Virchow JC, Prasse A, Naya I, Summerton L, Harris A. Zafirlukast improves asthma control in patients receiving high-dose inhaled corticosteroids. Amer J Respir Crit Care Med 162[2], 578–585. 2000. Ref Type: Journal (Full)

    Google Scholar 

  24. Robinson DS, Campbell D, Barnes PJ. Addition of leukotriene antagonists to therapy in chronic persistent asthma: a randomised double-blind placebo-controlled trial. Lancet 2001; 357(9273):2007–2011.

    Article  PubMed  CAS  Google Scholar 

  25. Bel EH, Desmet M, Rossing TH, Timmers MC, Dijkman JH, Sterk PJ. The effect of a specific oral PAF-antagonist, MK-287, on antigen-induced early and late asthmatic reactions in man. American Review Respiratory Disease 143, A811. 1991. Ref Type: Abstract

    Google Scholar 

  26. Wilkens JH, Wilkens H, Uffmann J, Bovers J, Fabel H, Frolich JC. Effects of a PAF-antagonist (BN 52063) on bronchoconstriction and platelet activation during exercise induced asthma. Br J Clin Pharmacol 1990; 29:85–91.

    Article  PubMed  CAS  Google Scholar 

  27. Bryan SA, Oconnor BJ, Matti S, Leckie MJ, Kanabar V, khan j et al. Effects of recombinant human interleukin-12 on eosinophils, airway hyper-responsivness, amd the late asthmatic response. Lancet 2000; 356:2149–2153.

    Article  PubMed  CAS  Google Scholar 

  28. Leckie MJ, ten Brincke A, khan j, Diamant Z, O’Connor BJ, Walls CM et al. Effects of an interleukin-5 blocking monoclonal antibody on eosinophils, airway hyperresponsiveness and the late asthmatic response. Lancet 2000; (In Press).

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2003 Springer Science+Business Media New York

About this chapter

Cite this chapter

Drazen, J.M. (2003). Leukotrienes in Asthma. In: Yazici, Z., Folco, G.C., Drazen, J.M., Nigam, S., Shimizu, T. (eds) Advances in Prostaglandin, Leukotriene, and other Bioactive Lipid Research. Advances in Experimental Medicine and Biology, vol 525. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-9194-2_1

Download citation

  • DOI: https://doi.org/10.1007/978-1-4419-9194-2_1

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-4831-3

  • Online ISBN: 978-1-4419-9194-2

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics