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


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


METHODS
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.


RESULTS
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, TNFalpha, IL-1beta, 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.


CONCLUSIONS
We conclude that inhaled ET-1 does not appear to stimulate an acute inflammatory response in asthma as assessed by differential cell count, TNFalpha, IL-1beta, NO2 and albumin concentrations in induced sputum.
Chalmers
G W
GW
Department of Respiratory Medicine, West Glasgow Hospitals University NHS Trust, UK.
MacLeod
K J
KJ
Thomson
L J
LJ
Little
S A
SA
Patel
K R
KR
McSharry
C
C
Thomson
N C
NC
D000328:Adult; D000418:Albumins / Q000187:drug effects / Q000378:metabolism; D001249:Asthma / Q000276:immunology*; D001985:Bronchial Provocation Tests; D016085:Bronchoconstrictor Agents / Q000494:pharmacology*; D002452:Cell Count / Q000187:drug effects; D018592:Cross-Over Studies; D016207:Cytokines / Q000187:drug effects* / Q000378:metabolism; D004311:Double-Blind Method; D019332:Endothelin-1 / Q000097:blood / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D008297:Male; D016210:Methacholine Chloride / Q000008:administration & dosage; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D013183:Sputum / Q000166:cytology*; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism
D000418:Albumins; D016085:Bronchoconstrictor Agents; D016207:Cytokines; D019332:Endothelin-1; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D016210:Methacholine Chloride; D009569:Nitric Oxide