title: Contribution of interleukin 18 to the development of infection-associated atopic dermatitis.
abstract: Atopic dermatitis (AD) has diverse etiologies. Some AD patients possess pathologically aberrant allergen-specific Th2 cells and resulting allergen-specific IgE, and exposure to the allergen exacerbates the skin lesions. This might be classified into the Th2-type AD. However, recent clinical studies revealed that the treatment with neutralizing anti-IgE monoclonal antibody does not always protect against AD, but rather has efficacy only in some variants of AD, perhaps Th2-type AD. This implicates that other factors might be involved. Interleukin (IL) 18 is a pleiotropic cytokine involved in both Th1-and Th2-type diseases. Many cell types including keratinocytes and dermal macrophages and dendritic cells are capable of producing IL-18. Our previous studies demonstrate that skin-specific overexpression of biologically active IL-18 causes AD-like skin lesions in mice. Loss of T cells and B cells cannot rescue these mice from AD-like lesions at all. Thus, aberrant IL-18 in the skin seems to be relevant to some types of AD. Furthermore, consecutive, topical application of Staphylococcus aureus product induces AD-like lesions in certain mice with a genetically impaired skin barrier. We found substantial efficacy of IL-18 blockade against this AD. Here, we review the recent finding that IL-18 is a possible therapeutic target of certain types of AD.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Tsutsui
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Mizutani
authors.forename: Kenji
authors.initials: K
authors.lastname: Nakanishi
mesh_terms: D000818:Animals; D020170:Caspase 1 / Q000235:genetics / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000209:etiology* / Q000276:immunology / Q000382:microbiology / Q000628:therapy; D006801:Humans; D007113:Immunity, Innate; D020382:Interleukin-18 / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D013207:Staphylococcal Skin Infections / Q000150:complications / Q000276:immunology; D013211:Staphylococcus aureus / Q000472:pathogenicity; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
chemical_list: D020382:Interleukin-18; D020170:Caspase 1