Increased Expression of IL-18 in Cutaneous Graft-versus-host Disease

Interleukin-18 (IL-18) is an 18-kDa cytokine produced by lipopolysaccharide (LPS)-activated macrophages or Kupffer cells. In addition, IL-18 is also produced by many different types of cells and tissues, including epidermal keratinocytes, the adrenal cortex, and the brain. IL-18 acts on the immune system to increase IFN-gamma production from T and NK cells to enhance NK cell cytotoxicity and to activate Th1 cell proliferation. It is considered that the tissue expression of cytokines and cell adhesion molecules such as ICAM-1 are common in graft-versus-host disease (GVHD). Recent evidence suggests that IL-18 is a cytokine relevant in the pathogenesis of GVHD. Despite the potential importance of IL-18 in GVHD, the distribution of IL-18 production in cutaneous GVHD has not been fully investigated. In this study, the expression of IL-18 in the cutaneous GVHD was investigated. Formalin-fixed, paraffin-embedded tissue sections were obtained, and immunohistochemical analysis was performed to detect IL-18 and ICAM-1 expression according to the acute and chronic GVHD. Immunohistochemical analysis confirmed the enhanced IL-18 expression levels in the early stage (grade 1) of acute GVHD and the late stage (sclerodermoid) of chronic GVHD compared to the other stages. In contrast, the ICAM-1 expression level was constant at all stages. Our findings indicate that IL-18 is a significant pathogenic indicator in cutaneous GVHD, and the tissue expression of IL-18 seems to be associated with the pathogenesis of acute and chronic GVHD.