Corticosteroids and interferons inhibit cytokine-induced production of IL-8 by human endothelial cells.
IL-8, secreted by endothelial cells at the site of inflammation, participates in recruitment and transmigration of leukocytes. IL-8 may also have pathophysiological consequences in inflammatory and immunological disorders. We have investigated the effect of interferons (IFNs) and glucocorticosteroids (GCs) on cytokine induced secretion and production of IL-8 by human umbilical endothelial cells (HUVEC). There was a low spontaneous secretion of IL-8 by unstimulated HUVEC which increased after 6 or 24 h of stimulation with the pro-inflammatory cytokines TNF-alpha or IL-1beta. IFN-gamma as well as the GCs, Dexamethasone and Budesonide, inhibited TNF-alpha induced IL-8 secretion in a dose-dependent manner. IFNs may have a general modulating effect, since IFN-alpha also inhibited the TNF-alpha-induced IL-8 secretion. There was a slight, but significant, increase in the content of intracellular IL-8 in stimulated HUVEC. However, there was no difference between stimulation with IL-1beta or TNF-alpha alone or in combination with IFNs or GCs, whereas inhibition of IL-8 secretion with monensin increased IL-8 content suggesting that IFNs and GCs inhibit synthesis rather than secretion of IL-8. In conclusion, IFNs or GCs may be useful for inhibiting IL-8 production by endothelial cells and could thus be used for therapeutic modulation of the inflammatory response.
Nyhlén
K
K
Department of Medicine and Care, Faculty of Health Science, Linköping, Sweden. kriny@imv.liu.se
Linden
M
M
Andersson
R
R
Uppugunduri
S
S
D019819:Budesonide / Q000276:immunology* / Q000494:pharmacology; D003907:Dexamethasone / Q000276:immunology* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology; D006801:Humans; D016898:Interferon-alpha / Q000276:immunology* / Q000494:pharmacology; D007371:Interferon-gamma / Q000276:immunology* / Q000494:pharmacology; D007375:Interleukin-1 / Q000276:immunology / Q000494:pharmacology; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000378:metabolism; D007424:Intracellular Fluid / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000494:pharmacology
D016898:Interferon-alpha; D007375:Interleukin-1; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D019819:Budesonide; D003907:Dexamethasone; D007371:Interferon-gamma