Clinical & Experimental Allergy

Ebastine inhibits T cell migration, production of Th2-type cytokines and proinflammatory cytokines

Authors

  • M. Nori,

    1. Division of Clinical Immunology, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo,
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  • S. Iwata,

    1. Division of Clinical Immunology, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo,
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  • Y. Munakata,

    1. Department of Molecular Diagnostics, Graduate School of Medicine, Tohoku University, Seiryo-cho, Aoba-ku, Sendai,
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  • H. Kobayashi,

    1. Division of Clinical Immunology, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo,
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  • S. Kobayashi,

    1. Division of Clinical Immunology, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo,
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  • Y. Umezawa,

    1. Second Department of Pathology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan,
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  • O. Hosono,

    1. Division of Clinical Immunology, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo,
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  • H. Kawasaki,

    1. Division of Clinical Immunology, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo,
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  • N. H. Dang,

    1. Department of Lymphoma/Myeloma, MD Anderson Cancer Center, Holcombe Boulevard, Houston, TX, USA, and
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  • H. Tanaka,

    1. Division of Clinical Immunology, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo,
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  • T. Shiohara,

    1. Department of Dermatology, Kyorin University, School of Medicine, Shinkawa, Mitaka-shi, Tokyo Japan
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  • C. Morimoto

    1. Division of Clinical Immunology, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo,
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Chikao Morimoto, Division of Clinical Immunology, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan. E-mail: morimoto@ims.u-tokyo.ac.jp

Summary

Background  Cytokine imbalance and cellular migration to inflammatory sites are critical components of allergic diseases. Redirecting cytokine imbalance and inhibiting cell migration therefore represent important therapeutic strategies for the treatment of these disorders.

Objectives  To study the in vitro effect of ebastine, a novel non-sedating H1 receptor antagonist, on cytokine secretion and migration of activated T cells, as well as production of pro-inflammatory cytokines by macrophages.

Methods  Peripheral T cells obtained from healthy volunteers were cultured in wells coated with the combination of anti-CD3 monoclonal antibody (mAb) and anti-CD26 mAb, anti-CD3 mAb and anti-CD28 mAb, or anti-CD3 mAb with PMA, in the presence or absence of ebastine. T cell proliferation and the production of cytokines were measured by [3H]thymidine incorporation assay and ELISA, respectively. In addition, transendothelial migration of T cells and production of pro-inflammatory cytokines by macrophages were examined.

Results  Ebastine inhibited T cell proliferation and the production of IL-4, IL-5, IL-6, and TNF-α by T cells under each co-stimulatory condition tested, whereas it exhibited no effect on the production of IL-2 or IFN-γ. In addition, T cell migration and the production of such pro-inflammatory cytokines as TNF-α and IL-6 by macrophages were inhibited by ebastine.

Conclusions  These results indicate that ebastine has a specific inhibitory effect on Th2-type cytokine production. Moreover, ebastine inhibited T cell migration and pro-inflammatory cytokine production by T cells and macrophages, suggesting that ebastine might be useful for the treatment of T cell-mediated allergic inflammatory disorders, including asthma, atopic dermatitis, and Th2-type autoimmune diseases.

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