IL-18 knockout alleviates atopic dermatitis-like skin lesions induced by MC903 in a mouse model

Abstract

Interleukin (IL)-18, a pro-inflammatory cytokine, plays an important role in a number of skin diseases. The aim of the present study was to investigate the role of IL-18 in the development of atopic dermatitis (AD). For this purpose, mice were divided into 4 groups (n=5/group) as follows: i) The wild-type (WT) controls; ii) IL18 knockout (KO) controls; iii) MC903-treated WT mice; and iv) MC903-treated KO mice. MC903 (4 nmol in ethanol) was topically applied daily for 15 consecutive days to the exposed skins of mice. AD-like symptoms and severity were evaluated by the scoring of AD (SCORAD). Serum immunoglobulin E (IgE) and thymic stromal lymphopoietin (TSLP) levels were determined with the use of an enzyme-linked immunosorbent assay. Immunohistochemistry was used to assess the expression of IL-1β, signal transducer and activator of transcription (STAT)3 and filaggrin (FLG) in the skin lesions. RT-qPCR was performed to assess the mRNA levels of IL-1β, IL-4, IL-9, STAT3, corticotropin-releasing hormone receptor (CRHR)1, CRHR2, TSLP and caspase-1 in the skin lesions. It was demonstrated that IL-18 may function as a pleiotropic pro-inflammatory cytokine in the development of AD-like lesions. IL-18 KO reduced aggravated AD-like lesions induced by MC903, in part by upregulating Th2 cytokines. IL-18 promoted the expression of FLG in the epidermis and CRHR2 in AD-like lesions, but downregulated the serum levels of IgE. On the whole, the findings of the present study demonstrate that IL-18 deficiency alleviates AD-induced lesions in mice.