Endothelin-1 production is associated with eosinophilic rather than neutrophilic airway inflammation

Endothelin-1 (ET-1) is a strong bronchoconstrictor which possesses proinflammatory properties and is claimed to be an important mediator in bronchial asthma. The present study was undertaken to investigate whether ET-I 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-I and tumour necrosis factor (TNP)-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-I 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-I levels was observed in the LPS model, while a substantial increase in the ET-I 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-l. This is in contrast to observations during an eosinophilic: airway inflammation, indicating a specific role of endothelin-l in lung inflammations dominated by eosinophils. In contrast to in vitro experiments, no evidence for induction of endothelin-l synthesis was observed by high levels of tumour necrosis factor-alpha in vivo.