ENDOTHELIN-1 STIMULATES HUMAN MONOCYTES IN-VITRO TO RELEASE TNF-ALPHA, IL-1-BETA AND IL-6

INCREASED plasma- and tissue levels of endothelin-1 (ET1) during infla mmatory diseases, have suggested a role of ET-1 in the pathophysiotogy of inflammatory reactions. The authors have studied the effect of ET- 1 on cytokine release from monocytes and monocyte-derived macrophages. ET-1 increased secretion of TNF-alpha, IL-1beta and IL-6 in a dose- a nd time-dependent manner. Optimal ET-1 concentration ranged from 0.01 to 1 nM. The maximal response was a 200 to 400% increase in cytokine r elease. A time-course study revealed that the pattern of cytokines ind uced by ET-1 was different in monocytes and macrophages, although an e arly increase in TNF-alpha was observed in both monocyte and macrophag e supernatants. In conclusion, ET-1 stimulates monocytes and macrophag es to release cytokines thereby demonstrating a potential role for ET- 1 in regulation of inflammatory responses.