| Co-Investigator(Kenkyū-buntansha) |
TUTUI Hiroko Hyogo College of Medicine, Associate Professor, 医学部, 助教授 (40236914)
OKAMURA Haruki Hyogo College of Medicine, Professor, 医学部, 教授 (60111043)
NAKANISHI Kenji Hyogo College of Medicine, Professor, 医学部, 教授 (60172350)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2001: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2000: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Research Abstract |
IL-18, an IL-1-like cytokine that requires cleavage with caspase-1 to become actiye, has strong ability to induce IFN-y production from T cells, B cells, NK cells, macrophages and dendritic cells, especially in combination with IL-12.In contrast, without IL-12, IL-18 has capacity to induce IL4 and/or IL-13 secretion from NK cells, basophils and mast cells in vitro. We have shown that in the presence of IL-3, IL-18 causes basophils and mast cells to produce large amounts of IL-4, IL-13 and histamine. We have also revealed that naive CD4+ Tcells cultured with IL-2 and IL-18 for 4 days express CD40L and produce IL-4 and IL-13.for induction of IL-18-induced IL-4 and IL-13 production, we need no antigenic stimulation, such as FceR cross-linkage or TCR engagement. Moreover, IL-18-administered mice or IL-18 transgenic mice which endogenously accumulated IL-18 had high serum IgE and this production is dependent on CD4+ T cells, IL-4 and Stat6.These results taken together indicate that IL18 induce allergic disorders, particularly intrinsic atopic diseases characterized by the absence of particular antigen. We call this IL-18-induced allergic disorder as an innate type allergic response.We also found that injection of ovalbumin-specific TCR transgenic BALB/c mice (DOll.10) with a goat-anti-mouse anti-IgD Ab increases IgE production without Th2 polarization. This anti-IgD-induced IgE production on DOll.10 has been revealed to depend upon the intrinsic IL18 and requires IL-4.Finally, we evaluated the serum IL-18 levels from patients with atopic dermatitis and found that IL-18 levels in the sera from patients with atopic dermatitis were significantly elevated compared to those from healthy volunteers. These results indicate that IL18 may be critically involved in regulation of Th2-independent IgE production
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