Open AccessIL-18, although antiallergic when administered with IL-12, stimulates IL-4 and histamine release by basophils
Author(s) -
Tomohiro Yoshimoto,
Hiroko Tsutsui,
Kouji Tominaga,
Katsuaki Hoshino,
Haruki Okamura,
Shizuo Akira,
William E. Paul,
Kenji Nakanishi
Publication year - 1999
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.96.24.13962
Subject(s) - histamine , immunoglobulin e , basophil , immunology , cytokine , mast cell , allergic inflammation , proinflammatory cytokine , interleukin 5 , stimulation , chemistry , interleukin 4 , biology , interleukin , inflammation , pharmacology , endocrinology , antibody
IL-18 is a proinflammatory cytokine that plays an important role in natural killer cell activation and T helper 1 (Th1) cell responses. Mast cells and basophils are major inducers and effectors of allergic inflammation. Here we show that basophils and mast cells derived by culture of bone marrow cells with IL-3 for 10 days express IL-18Rα chain and that basophils produce large amounts of IL-4 and IL-13 in response to stimulation with IL-3 and IL-18. Injection of IL-12 and IL-18 inhibits IgE production in helminth-infected wild-type mice and abolishes the capacity of their basophils to produce IL-4 and IL-13 in response to stimulation either with IL-3 and IL-18 or with FcɛR cross-linkage. By contrast, this combination of cytokines actually increases IgE levels in helminth-infected IFN-γ−/− mice and enhances IL-4 and IL-13 production by their basophils. Furthermore, injection of IL-18 alone enhances basophil production of IL-4 and histamine both in wild-type and IFN-γ−/− mice. Thus, IL-18 has the potential to stimulate basophils but, when given with IL-12, exhibits an antiallergic actionin vivo .