Effects of Interferons on the Production of Interleukin-6 and Interleukin-8 in Human Keratinocytes

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Abstract
Interferons (IFNs) originally described for antiviral activity have been reported to have pleiotropic effects, including the ability to induce interleukin-6 (IL-6) and IL-8 production in several cell types. IL-6 and IL-8 are proinflammatory cytokines and are known to be produced by a wide variety of cells, including human keratinocytes. In the present study, we sought to examine the effects of IFNs on IL-6 and IL-8 production from human keratinocytes. IFN-γ (10-50 ng/ml) induced IL-6 and IL-8 production dose dependently, but no induction of IL-6 or IL-8 was observed with either IFN-α or IFN-β. Because cytokines often work in a cascade fashion and keratinocytes are a source of primary cytokines, IL-1α, and tumor necrosis factor-α (TNF-α), we examined whether combined treatment with IFN-γ and these primary cytokines, IL-1α and TNF-α, had a synergistic effect on the production of IL-6 and IL-8. Combined treatment with IFN-γ and IL-1α induced 6-fold to 7-fold higher levels of IL-6 than IL-1α alone. Combined treatment with IFN-γ and TNF-α induced 11-fold to 12-fold higher levels of IL-6 than TNF-α alone. The same treatment induced 3-fold to 4-fold higher levels of IL-8 in both cases. These results suggest that IFN-γ is a positive regulator for the production of IL-6 and IL-8 from human keratinocytes and likely has an augmentative effect on skin inflammation.