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


G. W. Chalmers Department of Respiratory Medicine, West Glasgow Hospitals University NHS Trust, Glasgow G12 0YN, UK.



Endothelin (ET)-1 is a 21-amino acid peptide which has potent bronchoconstrictor activity. Animal studies show elevation of ET-1 during experimental airway inflammation, and inhibition of inflammation by endothelin-antagonists, suggesting pro-inflammatory activity for ET-1.


We wanted to assess any acute influence that bronchoconstrictor doses of inhaled ET-1 might have on cells, tumour necrosis factor (TNF)-α, interleukin (IL)-1β, nitrite (NO2) and albumin in induced sputum in asthma.


Bronchial challenge was performed using nebulized ET-1 (nebulized dose range 0.96–15.36 nmol) and placebo in 10 adult asthmatic subjects in a randomized double-blind placebo-controlled cross-over study. Sputum induction was performed 30 min and 4 h after placebo or ET-1 bronchial challenge.


All subjects experienced dose-dependent bronchoconstriction to inhaled 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, there was no change in sputum differential cell counts, TNFα, IL-1β, NO2 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. There was no fall in FEV1 at 4 h after ET-1 inhalation, suggesting that ET-1 inhalation is not associated with a late bronchoconstrictor response.


We conclude that inhaled ET-1 does not appear to stimulate an acute inflammatory response in asthma as assessed by differential cell count, TNFα, IL-1β, NO2 and albumin concentrations in induced sputum.