IL-18 Contributes to the Spontaneous Development of Atopic Dermatitis-like Inflammatory Skin Lesion Independently of IgE/stat6 Under Specific Pathogen-free Conditions

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2002 Aug 2

PMID 12151598

Citations 77

Authors

Hiroshi Konishi

Hiroko Tsutsui

Takaaki Murakami

Shizue Yumikura-Futatsugi

Kei-Ichi Yamanaka

Minoru Tanaka

Yohichiro Iwakura

Noboru Suzuki

Kiyoshi Takeda

Shizuo Akira

Kenji Nakanishi

Hitoshi Mizutani

Affiliations

Soon will be listed here.

Abstract

Atopic dermatitis (AD) is a pruritic inflammatory skin disease. Because IL-18 directly stimulates T cells and mast cells to release AD-associated molecules, Th2 cytokines, and histamine, we investigated the capacity of IL-18 to induce AD-like inflammatory skin disease by analyzing KIL-18Tg and KCASP1Tg, which skin-specifically overexpress IL-18 and caspase-1, respectively. They spontaneously developed relapsing dermatitis with mastocytosis and Th2 cytokine accumulation accompanied by systemic elevation of IgE and histamine. Stat6-deficient KCASP1Tg displayed undetectable levels of IgE but manifested the same degree of cutaneous changes, whereas IL-18-deficient KCASP1Tg evaded the dermatitis, suggesting that IL-18 causes the skin changes in the absence of IgE/stat6. KIL-18Tg and IL-1-deficient KCASP1Tg took longer to display the lesion than KCASP1Tg. Thus, AD-like inflammation is initiated by overrelease of IL-18 and accelerated by IL-1. Our present study might provide insight into understanding the pathogenesis of and establishing therapeutics for chronic inflammatory skin diseases including AD.

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