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 microg/L, and this decreased to 19.54 +/- 13.86 microg/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.

Department of Paediatrics University Hospital and Palacký University Olomouc Czech Republic

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Mol Pharmacol. 1999 Sep;56(3):657-63 PubMed

Life Sci. 1999;65(1):1-15 PubMed

Am J Physiol. 1997 May;272(5 Pt 1):L1021-4 PubMed

J Investig Allergol Clin Immunol. 1999 Mar-Apr;9(2):82-8 PubMed

Pulm Pharmacol. 1996 Apr;9(2):69-93 PubMed

Respir Med. 2002 Nov;96(11):901-6 PubMed

J Allergy Clin Immunol. 1999 Apr;103(4):630-6 PubMed

J Investig Allergol Clin Immunol. 2001;11(3):193-8 PubMed

Ann Allergy Asthma Immunol. 2002 Apr;88(4):370-3 PubMed

Int J Exp Pathol. 2000 Dec;81(6):429-37 PubMed

Ann Allergy Asthma Immunol. 2002 Apr;88(4):345-6 PubMed