Differential IL-10 receptor gene expression in acute versus chronic atopiceczema. Modulation by immunosuppressive drugs and cytokines in normal cultured keratinocytes

Objective and Design: The effects of the anticytokine interleukin 10 (IL-10 ) are mediated by specific receptors. In this study we examined the role of the IL-10 receptor (IL-10R) in the pathophysiology of atopic eczema. Materials and Methods: For this purpose we analyzed the expression of IL-10 R in the skin of patients with acute and chronic atopic eczema in compariso n to the expression in healthy individuals using in situ binding experiment s with fluorescently labeled IL-10 and semiquantitative reverse transcripta se-PCR specific for IL-10R1. In addition, we studied the influence of the T h2-associated cytokine interleukin-4 (IL-4), the Th1-associated gamma-inter feron (IFN-gamma), the immunosuppressive drug FK506, the H1-antagonist lora tadine and WA irradiation on the expression of IL-10R1 in cultured normal h uman keratinocytes. Results: We found that IL-10 receptor mRNA and protein are strongly downreg ulated in acute phase atopic lesions. Furthermore we could show that IL-4, IFN-gamma, FK506, loratadine and UVA enhance the mRNA levels of the IL-10R1 in vitro in normal cultured keratinocytes, We could also demonstrate resto red IL-10R1 mRNA levels in lesional atopic skin of a patient after UVA1 the rapy, Conclusions: Our results demonstrate for the first time that IL-10 receptor s may have a role in the pathogenesis of atopic eczema and its upregulation by FK506 and UVA could explain the therapeutic efficacy of these agents.