Inducer-specific bidirectional regulation of endothelial interleukin-8 production by thalidomide

Interleukin-8 (IL-8) is a potent neutrophil chemotaxin, which can also be p roduced by endothelial cells to facilitate leukocyte emigration. The aim of this study was to determine the effects of the anti-inflammatory drug thal idomide (THD) on chemotaxin release from endothelial cells. Human umbilical vein endothelial cells (HUVEC) were stimulated with tumor necrosis factor alpha (TNF alpha) or endotoxin (LPS) in the presence or absence of various concentrations of THD. Endothelium-derived interleukin-8 (eIL-8) in superna tants was measured using an enzyme-linked immunosorbent assay (ELISA) and b iological activity of the harvested eIL-8 was tested in Boyden chamber chem otaxis assays on PMNL. THD itself had no effect on eIL-8 release. Upon stim ulation with TNF alpha or LPS, HUVEC produced increased amounts of eIL-8 an d THD affected this process in a bidirectional manner, with augmentation of TNP alpha and inhibition of LPS-effects. Functionality of eIL-8 was confir med in chemotaxis experiments and by inhibition of chemotactic effects of s upernatants with anti-human IL-8 monoclonal antibodies. Results explain and emphasize immunomodulatory properties of THD in cytokine- and endotoxin-in duced inflammation and regulation of transendothelial migration. (C) 1999 E lsevier Science B.V. All rights reserved.