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.