INTERLEUKIN-10 INHIBITS IGE-MEDIATED NITRIC-OXIDE SYNTHASE INDUCTION AND CYTOKINE SYNTHESIS IN NORMAL HUMAN KERATINOCYTES

Human keratinocytes (HK) generate nitric oxide (NO) and proinflammator y mediators following activation with either IgE/anti-IgE immune compl exes or a combination of lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma). Recently, interleukin-10 (IL-10) has been shown to down- regulate various inflammatory responses and to be secreted by lymphocy tes and dendritic cells during skin inflammatory reactions. We show he re that IL-10 down-regulates the production of tumor necrosis factor ( TNF)-alpha and IL-6 by activated HK. Also, induction of inducible nitr ic oxide synthase (iNOS) expression in HK by IgE/anti-IgE or LPS/IFN-g amma 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 infla mmatory responses and may thus participate in the regulation of the sk in immune network.