Modulation of cytokine-induced production of IL-8 in vitro by interferons and glucocorticosteroids

Interleukin-8 (IL-8) has been implicated in the pathogenesis of inflammation and cancer. Intracellular levels of cytokine-induced IL-8 in human umbilical vein endothelial cells (HUVEC) were modulated using interferons and steroids to further elucidate their mechanism. Basal and cytokine-induced production of IL-8 was studied using a novel ELISA application, flow cytometry, and RT-PCR. The intracellular amount of IL-8 increased after 6-h stimulation with TNF-alpha (30%) or IL-1beta (55%) which was doubled when Golgi transport was disrupted using monensin. IFN-gamma decreased the intracellular amount of IL-8 by 60% in both unstimulated and TNF-alpha-stimulated cells, but only when secretion was blocked using monensin. Dexamethasone inhibited the TNF-alpha-induced production by 33%, but had no effect in unstimulated cells. Our study indicated that both, dexamethasone and IFN inhibit TNF-alpha-induced upregulation of IL-8 at the mRNA level. It could be speculated that they inhibit IL-8 production by affecting different gene regulatory mechanisms.