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

Endothelin-1 (ET-1) is a strong bronchoconstrictor which possesses proinfla mmatory properties and is claimed to be an important mediator in bronchial asthma. The present study was undertaken to investigate whether ET-I synthe sis, in an inflammation dominated by neutrophilic granulocytes, is as prono unced as previously demonstrated in an airway inflammation dominated by eos inophils. Moreover, the authors compared the production of ET-I and tumour necrosis factor (TNP)-alpha. in rat lungs following intratracheal instillat ion of either lipopolysaccharide (LPS) (neutrophilic inflammation) or Sepha dex (SDX) (eosinophilic). The lung tissue ET-1 messenger ribonucleic acid (mRNA) expression was not i ncreased in LPS treated animals whereas a six-fold increase was measured af ter 30 min in the SDX group (p<0.05). TNF-alpha mRNA signals increased earl y following LPS instillation, peaking at 2 h, whereas elevated TNF-alpha mR NA in the SDX model was observed at 24 h, The ET-I concentrations in bronch oalveolar lavage fluid (BALF) rose slightly, but significantly, 3 h after b oth LPS and SDX exposure. At 24 h no further rise in ET-I levels was observ ed 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 B ALF 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 endo thelin-l. This is in contrast to observations during an eosinophilic: airwa y inflammation, indicating a specific role of endothelin-l in lung inflamma tions dominated by eosinophils. In contrast to in vitro experiments, no evi dence for induction of endothelin-l synthesis was observed by high levels o f tumour necrosis factor-alpha in vivo.