Increased expression of IL-18 in cutaneous graft-versus-host disease

IL-27 Regulates IL-18 Binding Protein in Skin Resident Cells

“…IL-18 is highly expressed in chronic phases of skin diseases such as eczema, lupus erythematosus and psoriasis but also in e.g. lupus nephritis, chronic joint diseases and graft-versus-host disease [17], [24], [25], [26], [51], [52], [53], [54], [55], [56], [57]. It has been suggested that in allergic contact eczema IL-18 may act upstream of IL-1ß and TNFα in the induction of Langerhans cell migration [58] and its potential role in allergic contact dermatitis is highlighted by the fact that measurement of IL-18 has been suggested as a tool for the identification of substances with high sensitising potential [51].…”

Granzyme B is a novel interleukin-18 converting enzyme

“…Thus, lymphocytes accumulated in skin lesions may participate in both injury of keratinocytes and release of IL-18 in the microenvironment. Acute GVHD in patients and mouse models is characterized by the presence of apoptotic changes of epidermal keratinocytes, concomitantly with elevated serum levels of GrB and IL-18 [16,17]. We had demonstrated that natural GrB, independently of capsase-1, from cultured CD8+ T cell lysate is capable of cleaving proIL-18 into its mature IL-18 form, and that this cleavage is abolished by the addition of the GrB-specific inhibitor Z-AAD-CMK (Fig.…”

“…Thus, GrB is a critical enzyme for activating multiple processes leading to cell death. Indeed, GrB is essential for the development of IL-18-associated inflammatory disease, such as acute graft-versus-host disease (GVHD) [16,17], allergic disease [18,19], inflammatory bowel disease [20,21], renal transplantation [22,23], and autoimmune disease [24]. These observations raised the hypothesis that GrB injected into target cells serves as a processing enzyme for stored proIL-18 as well as an inducer of apoptotic cell death.…”

Immunohistochemical characterization of cutaneous drug eruptions by STI571

“…The effect of IL-18 on the immune system includes the induction of IFN-g secretion from Th1 cells, enhancing NK cell activity, and enhancement of proliferation of the activated T cells [6,7]. Recently, we found that the level of IL-18 expression is increased in severe inflammatory tissue damage, including GVHD [7][8][9]. In this study, skin specimens from drug eruption by STI571 and antibiotics were examined for the expression of IL-18, IL-1b and ICAM-1.…”