Decreased production of endothelin-1 in asthmatic children after immunotherapy

Endothelin-1 (ET-1) is an endothelium-derived peptide that may be the most potent vasoconstrictor and bronchoconstrictor yet known. To investigate the role of ET-1 in the pathogenesis of bronchial asthma and the effect of immunotherapy (IT) on endothelin production, we measured the in vivo and in vitro production of ET-1 in 24 asthmatic children before and after specific allergen IT for 2 years as well as in age-matched healthy controls. Our results showed that both the plasma concentrations and in vitro production of ET-1 from the supernatants of cultured mononuclear cells (MNCs) were significantly higher in asthmatic children than in control subjects. The mean plasma levels of ET-1 in asthmatic children before or after IT were significantly higher than in controls (49.4 +/- 26.5 and 30.6 +/- 20.7 ng/L vs. 13.2 +/- 8.5 ng/L, p < 0.05 and p < 0.01, respectively). When stimulated with phytohemagglutin (PHA) (1 microgram/ml) or mite extract (10 micrograms/ml) for 3 days, mononuclear cell from asthmatic children before IT produced significantly higher ET-1 than did those after IT (31.8 +/- 23.0 vs. 18.0 +/- 15.7 ng/L, stimulated with mite, and 67.9 +/- 22.4 vs. 25.0 +/- 13.3 ng/L, stimulated with PHA). The decreased production of ET-1 in MNCs culture supernatant of asthmatic children after IT indicated that immunotherapy may result in an immune nonresponsive state, which may reverse the abnormal secretory pattern of ET-1 production in asthmatic children and partly account for its clinical effectiveness in treating atopic patients.