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.
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 asthmapatients. 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, asthmapatients 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.
Authors: S M van Schaik; D A Tristram; I S Nagpal; K M Hintz; R C Welliver; R C Welliver Journal: J Allergy Clin Immunol Date: 1999-04 Impact factor: 10.793
Authors: H M Sarau; R S Ames; J Chambers; C Ellis; N Elshourbagy; J J Foley; D B Schmidt; R M Muccitelli; O Jenkins; P R Murdock; N C Herrity; W Halsey; G Sathe; A I Muir; P Nuthulaganti; G M Dytko; P T Buckley; S Wilson; D J Bergsma; D W Hay Journal: Mol Pharmacol Date: 1999-09 Impact factor: 4.436