Skip to main content
SpringerLink
Log in

Montelukast Decreases Plasma Endothelin-1 and Serum Eosinophil Cationic Protein Levels in Paediatric Atopic Asthma

  • Original Research Article
  • Published:
Clinical Drug Investigation Aims and scope Submit manuscript

Abstract

Background and objective: Endothelin-1 (ET-1) is produced by vascular endothelial cells and epithelial cells, T-lymphocytes and phagocytes. Increased ET-1 levels have been demonstrated in the bronchial epithelium of asthma patients. In vitro, ET-1 stimulates mucus secretion, activates proinflammatory cells — macrophages and mast cells — and serves as a mitogenic stimulus for fibroblasts and smooth muscle. In addition, ET-1 activates phospholipase 2. Compared with healthy individuals, asthma patients have increased ET-1 levels during an attack and following stabilisation. Our study was designed to examine plasma ET-1 (P-ET) levels in paediatric atopic patients newly diagnosed with persistent mild bronchial asthma and 1 month after initiation of montelukast therapy.

Methods: Patients’ histories were examined, and their blood eosinophil leucocyte count and levels of total serum immunoglobulin E (S-IgE), serum eosinophil cationic protein (S-ECP) and P-ET were determined. Thirty-six patients with persistent mild bronchial asthma were treated with the leukotriene receptor antagonist montelukast, administered once a day for 4 weeks. Second P-ET and S-ECP level determinations were made 4 weeks later with all the children included in the study. P-ET levels were also determined in a group of 27 healthy children who had no atopy in their medical histories and were taking no drugs (including montelukast), and who served as controls.

Results: The mean ± SD pretreatment P-ET level in the 36 study children was 11.542 ± 6.408 pg/L, and this decreased to 5.636 ± 4.419 pg/L after 1 month’s therapy with montelukast (statistically significant difference; p < 0.0001). Both of these values were significantly higher (p < 0.0001 and p < 0.031, respectively) than the mean level in the control group of 27 children (3.543 ± 2.497 pg/L). The mean pretreatment S-ECP level was 35.78 ± 19.58 μg/L, and this decreased to 19.54 ± 13.86 μg/L after 1 month’s therapy (p < 0.001).

Conclusions: This study demonstrated a decrease in P-ET levels in children with mild asthma receiving montelukast. This indicates a reduction in the severity of the inflammatory response and, hence, provides evidence for the anti-inflammatory effect of montelukast. Monitoring both ET-1 and ECP levels at regular follow-up may be useful in assessing these two facets of activity of chronic inflammation in bronchial asthma.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Table I
Fig. 1

Similar content being viewed by others

References

  1. Borish L. Endothelin-1: a useful marker for asthmatic inflammation? Ann Allergy Asthma Immunol 2002 Apr; 88(4): 345–6

    Article  PubMed  Google Scholar 

  2. Carratu P, Scuri M, Stybio JI, et al. ET-1 induces mitogenesis in ovine airway smooth muscle cells via ETA and ETB receptors. Am J Physiol 1997 May; 272 (5 Pt 1): L1021–4

    PubMed  CAS  Google Scholar 

  3. Dube J, Charlie J, Dube C, et al. Synergistic action of endothelin (ET)-l on the activation of bronchial fibroblast isolated from normal and asthmatic subjects. Int J Exp Pathol 2000 Dec; 81(6): 429–37

    Article  PubMed  CAS  Google Scholar 

  4. Goldie RG, Henry PJ. Endothelins and asthma. Life Sci 1999; 65(1): 1–15

    Article  PubMed  CAS  Google Scholar 

  5. NHLBI/WHO Workshop Report: Global strategy for asthma management and prevention. Issued January 1995. NIH Publication No. 02-3659. Updated 2002

  6. Zapletal A, Zemanek M, Paul T. Lung function in children and adolescents: methods and reference values. In Progress in Respiratory Disease. Basel: Herzog 1987

  7. Hay DWP, Compton CH. Endothelin antagonists. In: Hansel TT, Barnes PJ, editors. New drugs for asthma, allergy and COPD. Prog Respir Res 2001; 31: 141–4

    Chapter  Google Scholar 

  8. EL-Gamal Y, Hossny E, Awwad K, et al. Plasma endothelin-1 immunoreactivity in asthmatic children. Ann Allergy Asthma Immunol 2002 Apr; 88(4): 370–3

    Article  PubMed  Google Scholar 

  9. Goldie RG, Knott PG, Carr M, et al. The endothelins in the pulmonary system. Pulm Pharmacol 1996 Apr; 9(2): 69–93

    Article  PubMed  CAS  Google Scholar 

  10. Grebski E, Wu J, Wuthrich B, et al. Does eosinophil cationic protein in sputum and blood reflect bronchial inflammation and obstruction in allergic asthmatics? J Investig Allergol Clin Immunol 1999; 9: 82–8

    PubMed  CAS  Google Scholar 

  11. Holla LL, Vasku A, Lzakovic V, et al. Variants of endothelin-1 gene in atopic disease. J Investig Allergol Clin Immunol 2001; 11(3): 193–8

    PubMed  CAS  Google Scholar 

  12. Dworski R, Szczeklik A, Prokop A, et al. Urinary levels of endothelin-1 increase in patients with aspirin-induced asthma after inhaled challenge with asthma [abstract]. Am J Respir Crit Care Med 1998; 157: A718

    Google Scholar 

  13. Welliever II RC, Welliever RC. Increased production of IFN-gamma and cysteinyl leukotrienes in virus-induced wheezing. J Allergy Clin Immunol 1999 Apr; 103(4): 630–6

    Article  Google Scholar 

  14. Sarau HM, Ames RS, Chambers J, et al. Identification, molecular cloning, expression, and characterization of cysteinyl leukotriene receptor. Mol Pharmacol 1999 Sep; 56(3): 657–63

    PubMed  CAS  Google Scholar 

  15. Finsnes F, Lyberg T, Christensen G, et al. Leukotriene antagonism reduces the generation of endothelin-1 and inteferongama and inhibits eosinophilic airway inflammation. Respir Med 2002; 96(11): 901–6

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by MSM grant 6198959216 and MSD, s.r.o Czech Republic. The authors have no potential conflicts of interest that are directly relevant to the contents of this study.

Author information

Authors and Affiliations

  1. Department of Paediatrics, Palacký University Medical School and University Hospital, Puškinova 6, 775 20, Olomouc, Czech Republic

    Frantisek Kopřiva & Martin Zápalka

  2. Laboratory of Experimental Medicine, University Hospital and Palacký University, Olomouc, Czech Republic

    Anna Janošťáková & Marián Hajduch

  3. Department of Immunology, University Hospital and Palacký University, Olomouc, Czech Republic

    Szotkowská Jarmila

Authors
  1. Frantisek Kopřiva
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anna Janošťáková
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Szotkowská Jarmila
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Martin Zápalka
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Marián Hajduch
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Frantisek Kopřiva.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kopřiva, F., Janošťáková, A., Jarmila, S. et al. Montelukast Decreases Plasma Endothelin-1 and Serum Eosinophil Cationic Protein Levels in Paediatric Atopic Asthma. Clin. Drug Investig. 26, 351–356 (2006). https://doi.org/10.2165/00044011-200626060-00006

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00044011-200626060-00006

Keywords

Search

Navigation