Human keratinocytes constitutively produce but do not recess interleukin-18

Background Interleukin (IL)-18 is a potent immunomodulatory cytokine which promotes T-helper (Th) 1 and cytotoxic responses. IL-18 signals through a t wo-chain receptor (IL-18R and accessory protein-like subunit, AcPL), and an inhibitory molecule, IL-18 binding protein (IL-18BP), has recently been ch aracterized. Objectives The aim of the present study was to define the production of IL- 18 and its receptor by human keratinocytes. Methods The presence of IL-18 was determined using polymerase chain reactio n in human keratinocyte cultures with or without treatment with potential i nducers, Results The IL-18 gene was constitutively transcribed by primary human kera tinocytes and cell lines and was not significantly altered following exposu re to IL-1 beta, tumour necrosis factor-alpha, interferon (IFN)-gamma, phor bol myristate acetate or nickel sulphate, IL-18 protein was constitutively present at high levels in keratinocyte lysates and was detectable in supern atants exclusively in the unprocessed, 24-kDa form. Cytokine exposure faile d to induce any change in protein levels or processing. Primary keratinocyt es produced IL-18R and AcPL constitutively at the mRNA level, in addition t o low levels of IL-18BP, which was transcriptionally inducible following tr eatment with IFN-gamma. Conclusions These findings demonstrate that IL-18 is constitutively synthes ized by human keratinocytes and is released in an unprocessed form in vitro . Release of IL-18 by human keratinocytes may permit them to regulate IFN-g amma production during cutaneous inflammatory responses and suggests that I L-18 may represent an attractive target for immunomodulatory intervention i n Th1-mediated inflammatory diseases such as psoriasis.