Interleukin‐10 inhibits IgE‐mediated nitric oxide synthase induction and cytokine synthesis in normal human keratinocytes

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Abstract
Human keratinocytes (HK) generate nitric oxide (NO) and proinflammatory mediators following activation with either IgE/anti‐IgE immune complexes or a combination of lipopolysaccharide (LPS) and interferon‐γ (IFN‐γ). Recently, interleukin‐10 (IL‐10) has been shown to down‐regulate various inflammatory responses and to be secreted by lymphocytes and dendritic cells during skin inflammatory reactions. We show here that IL‐10 down‐regulates the production of tumor necrosis factor (TNF)‐α and IL‐6 by activated HK. Also, induction of inducible nitric oxide synthase (iNOS) expression in HK by IgE/anti‐IgE or LPS/IFN‐γ is significantly reduced by the addition of IL‐10. This effect is dose dependent and correlates with reduction of iNOS mRNA production and enzyme level. Therefore, IL‐10 down‐regulates NO‐mediated HK inflammatory responses and may thus participate in the regulation of the skin immune network.