RT Journal Article
SR Electronic
T1 Endothelin-1 production is associated with eosinophilic rather than neutrophilic airway inflammation
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 743
OP 750
DO 10.1034/j.1399-3003.2000.15d19.x
VO 15
IS 4
A1 Finsnes, F
A1 Skjonsberg, OH
A1 Lyberg, T
A1 Christensen, G
YR 2000
UL http://erj.ersjournals.com/content/15/4/743.abstract
AB Endothelin-1 (ET-1) is a strong bronchoconstrictor which possesses pro-inflammatory properties and is claimed to be an important mediator in bronchial asthma. The present study was undertaken to investigate whether ET-1 synthesis, in an inflammation dominated by neutrophilic granulocytes, is as pronounced as previously demonstrated in an airway inflammation dominated by eosinophils. Moreover, the authors compared the production of ET-1 and tumour necrosis factor (TNF)-alpha in rat lungs following intratracheal instillation of either lipopolysaccharide (LPS) (neutrophilic inflammation) or Sephadex (SDX) (eosinophilic). The lung tissue ET-1 messenger ribonucleic acid (mRNA) expression was not increased in LPS treated animals whereas a six-fold increase was measured after 30 min in the SDX group (p<0.05). TNF-alpha mRNA signals increased early following LPS instillation, peaking at 2 h, whereas elevated TNF-alpha mRNA in the SDX model was observed at 24 h. The ET-1 concentrations in bronchoalveolar lavage fluid (BALF) rose slightly, but significantly, 3 h after both LPS and SDX exposure. At 24 h no further rise in ET-1 levels was observed in the LPS model, while a substantial increase in the ET-1 concentration was measured in the SDX group (p<0.05). The TNF-alpha concentrations in BALF rose considerably at 3 h in the LPS group, but was nearly abolished at 24 h. In SDX challenged animals however, an increase in BALF-TNF-alpha did not occur until 24 h postchallenge. In conclusion, intratracheal instillation of lipopolysaccharide, leading to a purely neutrophilic lung inflammation, does not induce synthesis of endothelin-1. This is in contrast to observations during an eosinophilic airway inflammation, indicating a specific role of endothelin-1 in lung inflammations dominated by eosinophils. In contrast to in vitro experiments, no evidence for induction of endothelin-1 synthesis was observed by high levels of tumour necrosis factor-alpha in vivo.