Sputum cellular and cytokine responses to inhaled endothelin-1 in asthma

Background Endothelin (ET)-1 is a 21-amino acid peptide which has potent br onchoconstrictor activity. Animal studies show elevation of ET-1 during exp erimental airway inflammation, and inhibition of inflammation by endothelin -antagonists, suggesting pro-inflammatory activity for ET-1. Objective We wanted to assess any acute influence that bronchoconstrictor d oses of inhaled ET-1 might have on cells, tumour necrosis factor (TNF)-alph a, interleukin (IL)-1 beta, nitrite (NO2) and albumin in induced sputum in asthma. Methods Bronchial challenge was performed using nebulized ET-1 (nebulized d ose range 0.96-15.36 nmol) and placebo in 10 adult asthmatic subjects in a randomized double-blind placebo-controlled cross-over study. Sputum inducti on was performed 30 min and 4 h after placebo or ET-1 bronchial challenge. Results All subjects experienced dose-dependent bronchoconstriction to inha led ET-1 with a mean (range) PC15 forced expiratory volume in 1 s (FEV1) to ET-1 of 9.45 (1.2-21.7) nmol. Comparing ET-1 with placebo inhalation, ther e was no change in sputum differential cell counts, TNF alpha, IL-1 beta, N O2 or albumin at 30 min or 4 h after inhalation, nor was there a difference in these parameters at 4 h compared with 30 min after ET-1 inhalation. The re was no fall in FEV1 at 4 h after ET-1 inhalation, suggesting that ET-1 i nhalation is not associated with a late bronchoconstrictor response. Conclusions We conclude that inhaled ET-1 does not appear to stimulate an a cute inflammatory response in asthma as assessed by differential cell count , TNF alpha, IL-1 beta, NO2 and albumin concentrations in induced sputum.