Exacerbated and Prolonged Allergic and Non-Allergic Inflammatory Cutaneous Reaction in Mice with Targeted Interleukin-18 Expression in the Skin

Abstract

Interleukin 18 induces both T helper 1 and T helper 2 cytokines, proinflammatory cytokines, chemokines, and IgE and IgG1 production. A role of interleukin 18 in inflammatory cutaneous reactions is still unclear, however. Here we generated keratin 5/interleukin 18 transgenic mice overexpressing mature murine interleukin 18 in the skin using a human keratin 5 promoter. In the contact hypersensitivity model, trinitrochlorobenzene elicited a stronger ear swelling in keratin 5/interleukin 18 transgenic mice compared with control littermate wild-type or immunoglobulin/interleukin 18 transgenic mice in which mature interleukin 18 was expressed by B and T cells under the control of the immunoglobulin promoter. Application of an irritant, croton oil, induced stronger and more sustained ear swelling in keratin 5/interleukin 18 transgenic mice than in immunoglobulin/interleukin 18 transgenic or wild-type mice. Repetitive topical application (weekly for six consecutive weeks) of trinitrochlorobenzene to their ears also elicited a stronger cutaneous inflammation in keratin 5/interleukin 18 transgenic mice than seen in immunoglobulin/interleukin 18 transgenic or wild-type mice. After these six trinitrochlorobenzene applications, the expression of interferon-gamma, interleukin-4, and CCL20 mRNA in the ear tissue was increased and dermal changes, such as acanthosis and eosinophilic, neutrophilic, and mast cell infiltration, were greater in keratin 5/interleukin 18 transgenic mice than in wild-type mice. Furthermore, the repetitive application elicited a significant increase in serum IgE levels and the number of B cells in the draining lymph node in keratin 5/interleukin 18 transgenic mice. These results suggest that overexpression of interleukin 18 in the skin aggravates allergic and nonallergic cutaneous inflammation, which is accompanied by high expression of T helper 1 and T helper 2 cytokines and chemokines in the skin.

IL‐1, IL‐18, and IL‐33 families of cytokines

“…The role of IL-18 has not been examined in models of psoriasis. However, it has been shown that transgenic mice overexpressing IL-18 develop a severe and persisting skin reaction in response to topical irritants (146).…”

Correlation of Decreased Survival and IL-18 in Bone Metastasis

“…In addition, associations between levels of some Th1 cytokines, such as IL-2 (4) and , and prognosis in several cancers have been reported, suggesting that serum levels of specific cytokines can be used as prognostic makers in patients with some cancers. (6,(9)(10)(11)(12)(13)(14). (21).…”

Increased Interleukin-18 in the Gingival Tissues Evokes Chronic Periodontitis after Bacterial Infection

“…Additionally, it has been reported that overexpression of IL-18 in the skin aggravates allergic and non-allergic cutaneous inflammation (Kawase et al 2003). These findings suggest that excessive IL-18 in the gingival tissues could be a key stimulator of periodontal disease.…”

“…IL-18Tg mice with a C57BL/6N background (8-10 weeks old) were kindly provided by T. Hoshino (Kurume University, Kurume, Japan). In these mice, keratinocytes express mouse IL-18 fused to the signal peptide of the mouse immunoglobulin κ-chain, under the control of the human keratinocyte K5 promoter (Kawase et al 2003). Age-matched wild-type (WT) C57BL/6N mice were purchased from Charles River Japan (Yokohama, Japan).…”