- Paper Report
- Open Access
ET-1 and cytokines in airway inflammation
- Kristen Page1
© Biomed Central Ltd 2001
- Received: 11 April 2001
- Accepted: 18 September 2001
- Published: 18 September 2001
- Asthma, BAL, bosentan, cytokine, endothelin, inflammation
Endothelin (ET)-1 has been implicated in the development of eosinophilic airway inflammation although its role is unknown. It has been demonstrated to increase both mucus secretion and vascular leakage, and has been detected in bronchoalveolar lavage (BAL) fluid in asthmatics. The aim of this study was to determine the role of ET-1 in the synthesis of other inflammatory cytokines, including tumor necrosis factor (TNF)-a, interleukin (IL)-1?, IL-4, IL-8, interferon (IFN)-? and leukotriene (LT) B4.
ET-1 mRNA increased 15 min following Sephadex (SDX) provocation, which correlated with the early phase of inflammation, and declined after 2 h. Increases in the mRNA levels of IL-1?, IL-8 and TNF-a mRNA followed 12-24 h later. IFN-? and IL-4 mRNA levels were not detectable in the lung tissues during the course of this study. A substantial amount of LT B4 was detected in the BAL fluid 15 min following provocation and was maintained for 2 h. IL-8 and TNF-a protein expression in BAL fluid was biphasic, with peaks at 3 h and 24 h. The concentration of ET-1 in the BAL fluid did not increase until 6 h following SDX provocation, this delay may be due to abluminal secretion of ET-1. Rats were treated with bosentan, a highly specific ET antagonist, prior to SDX provocation. As expected if synthesis of ET-1 preceded the synthesis of other proinflammatory cytokines, bosentan pretreatment attenuated expression of TNF-a, IL-4, IL-1?, IL-8 and IFN-? in BAL fluid.
Intratracheal installation of SDX, male Wistar rats, BAL, ELISA, mRNA isolation, radioimmunoassay