title: Endothelin-1 production is associated with eosinophilic rather than neutrophilic airway inflammation.
abstract: 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.
authors.affiliation: Dept of Pulmonary Medicine, Institute for Experimental Medical Research, Ulleval Hospital, Oslo, Norway.
authors.forename: F
authors.initials: F
authors.lastname: Finsnes
authors.forename: O H
authors.initials: OH
authors.lastname: Skjønsberg
authors.forename: T
authors.initials: T
authors.lastname: Lyberg
authors.forename: G
authors.initials: G
authors.lastname: Christensen
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D001985:Bronchial Provocation Tests; D001991:Bronchitis / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D003911:Dextrans / Q000494:pharmacology; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000032:analysis / Q000096:biosynthesis*; D004802:Eosinophilia / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000473:pathology*; D008297:Male; D011336:Probability; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D018709:Statistics, Nonparametric; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000096:biosynthesis*
chemical_list: D003911:Dextrans; D019332:Endothelin-1; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; C025614:sephadex