Effects of interleukin 4 on the production of interleukin 6 in human keratinocytes

Background: The human keratinocyte can synthesize interleukin 6 (IL-6) under certain conditions, and the IL-6 synthesis is inhibited by interleukin 4 (IL-4) in the human monocyte. Objective: To find out what kind of stimulating agents can induce the IL-6 production and whether IL-4 affects the production of IL-6 in the human cultured keratinocytes. Methods: We stimulated the keratinocytes with either lipopolysaccharide (LPS), fetal bovine serum (FBS), human recombinant interferon-γ (IFN-γ) to induce the IL-6 production, and treated the keratinocytes, which stimulated either with 10% FBS or human recombinant IFN-γ, with human recombinant IL-4. Results: The LPS stimulation resulted in no increase of IL-6 levels in the keratinocyte supernatants. When the keratinocytes were stimulated either with 1%, 5%, 10% FBS with or without 5 μg/ml LPS, significantly increased amounts of IL-6 were detected. The level of IL-6 in the keratinocytes treated with the human recombinant IFN-γ increased, too. The human recombinant IL-4 downregulates the secretion of IL-6 by the keratinocytes which were activated either with 10% FBS or human recombinant IFN-γ. Conclusion: We have shown that it is possible to induce the IL-6 synthesis by stimulating the keratinocytes and that human recombinant IL-4 profoundly inhibits the synthesis of IL-6. So we suggest that there may be a cytokine network which regulates the primary immune response in the skin.