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2006 Fiscal Year Final Research Report Summary

The development of 2nd generated leukocytapheresis to remove phathological immune cells in inflammatory bowel diseases

Research Project

Project/Area Number 17590622
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionTokyo Medical and Dental University

Principal Investigator

ARAKI Akihiro  Tokyo Medical and Dental University, Department of Gastroenterology and Hepatology, Instructor, 医学部附属病院, 助手 (80361690)

Co-Investigator(Kenkyū-buntansha) KANAI Takanori  Tokyo Medical and Dental University, Department of Gastroenterology and Hepatology, Assistant Professor, 医学部附属病院, 講師 (40245478)
OOOKA Shinya  Tokyo Medical and Dental University, Department of Gastroenterology and Hepatology, Instructor, 医学部附属病院, 助手 (90361691)
WATANABE Mamoru  Tokyo Medical and Dental University, Department of Gastroenterology and Hepatology, Professor, 大学院医歯学総合研究科, 教授 (10175127)
Project Period (FY) 2005 – 2006
Keywordsinflammatory bowel disease / ulcerative colitis / Crohn's disease / leukocytapheresis
Research Abstract

Leukocytapheresis using a leukocyte removal filter (known as lymphocytapheresis, LCAP) has been applied to the treatment of ulcerative colitis (UC) in recent years. We here aim to clarify how LCAP therapy modifies inflammatory responses by modulating circulating monocytes and lymphocytes. Mononuclear cells were isolated from blood before and after LCAP treatment, and expression profiles of various immune cells (naive vs. memory, regulatory CD4^+CD25^<bright> vs. non-regulatory CD4^+CD25^- T cells, CD14^+CD16^- vs. CD14^<dull>CD16^+ monocytes, and effector-memory CD4^+CD45RO^+CD62L^- vs. central-memory CD4^+CD45RO^+CD62L^+ cells) were evaluated by FACS. To assess immunological differences between CD14^+CD16^- and CD14^<dull>CD16^+ monocytes, expression of TNF-α, IL-6, IL-12, IL-18, TLR2, TLR4, and other activation markers including HLA-DR, CD80 and CD86, as well as cytokine profiles were analyzed. We found that LCAP treatment selectively removed CD14^<dull>CD16^+ monocytes, which prefer … More entially produce proinflammtory TNF-α and IL-12, and express HLA-DR, CD80, CD86, and TLR2 compared with the major fraction of CD14^+CD16^- monocytes. In addition, the ratio was significantly lower after LCAP therapy. However, the CD4^+CD25^<bright>/total CD4^+ ratio did not change. The findings reveal the real target of proinflammatory CD14^<dull>CD16^+ monocytes, removed during LCAP treatment for UC, and that LCAP might be used as an extracorporeal anti-TNF-α/IL-12 therapy, expanding the clinical applications of this procedure to include the treatment of Crohn's disease. Furthermore, the fact that LCAP selectively removed effector-memory type of CD4^+ T cells rather than central-memory CD4^+ T cells indicates that LCAP selectively removes gut-homing colitotgenic CD4^+ T cells. Taken together, we propose that lymphocytapheresis rank up extracorporeal therapy not only to shut down the circulation of colitogenic immune cells in UC, but also possibly to decrease side effects that are usually seen in conventional drug therapies. Now, we are developing 2^<nd> generated absorbing fibers that are conjugated commercially used anti-TNF-α mAb to remove TNF-α-expressing cells more selectively and effectively. Less

  • Research Products

    (5 results)

All 2007 2006

All Journal Article (5 results)

  • [Journal Article] Extracorporeal elimination of TNF-alpha-producing CD14^<dull> CD16^+monocytes in leukocytapheresis therapy for ulcerative colitis.2007

    • Author(s)
      Kanai T, Makita S, Kawamura T, Kawamura T, Nemoto Y, Kubota D, Nagayama K, Totsuka T, Watanabe M
    • Journal Title

      Inflam Bowel Dis. 13・3

      Pages: 284-290

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Extracorporeal elimination of TNF-alpha-producing CD14^<dull>CD16^+ monocytes in leukocytapheresis therapy for ulcerative colitis.2007

    • Author(s)
      Kanai T, Makita S, Kawamura T, Kawamura T, Nemoto Y, Kubota D, Nagayama K, Totsuka T, Watanabe M.
    • Journal Title

      Inflam Bowel Dis. 13(3)

      Pages: 284-290

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] The logics of leukocytapheresis as a natural biological therapy for inflammatory bowel disease2006

    • Author(s)
      Kanai T, Hibi T, Watanabe M
    • Journal Title

      Expert Opin Biol Ther. 6・5

      Pages: 453-466

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] 新しい工夫・ダブルオーバーチューブ法によるダブルバルーン内視鏡の報告2006

    • Author(s)
      荒木昭博, 他
    • Journal Title

      Progress of Digestive Endoscopy. 68・2

      Pages: 53-57

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] The logics of leukocytapheresis as a natural biological therapy for inflammatory bowel disease.2006

    • Author(s)
      Kanai T, Hibi T, Watanabe M.
    • Journal Title

      Expert Opin Biol Ther. 6(5)

      Pages: 453-466

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2008-05-27  

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