Extracorporeal elimination of TNF-α-producing CD14 dullCD16+ monocytes in leukocytapheresis therapy for ulcerative colitis

Takanori Kanai, Shin Makita, Takahiro Kawamura, Yasuhiro Nemoto, Daisuke Kubota, Kazuyoshi Nagayama, Teruji Totsuka, Mamoru Watanabe

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29 Citations (Scopus)

Abstract

Background: In recent years leukocytapheresis using a leukocyte removal filter (known as lymphocytapheresis, LCAP) has been applied to the treatment of various autoimmune diseases including ulcerative colitis (UC). In the present study we aimed to clarify how LCAP therapy modifies inflammatory responses by modulating circulating TNF-α-producing monocytes. Methods: Mononuclear cells were obtained from blood before and after the first treatment, and the expression profiles of various immune cells (naive versus, memory, regulatory CD4+CD25bright versus non-regulatory CD4 +CD25- T cells, and CD14+CD16- versus CD14dullCD16+ monocytes) were assessed. To evaluate immunological differences between CD14+CD16- and CD14dullCD16+ monocytes, the expression of TNF-α, IL-6, IL-12, IL-10, IL-18, surface toll-like receptor 2 (TLR2), TLR4, and other activation markers including HLA-DR, CD80 and CD86, as well as cytokine profiles, were analyzed. Results: LCAP treatment selectively removed CD14 dullCD16+ monocytes, which preferentially produce TNF-α and IL-12 and express HLA-DR, CD80, CD86, and TLR2, compared with the major fraction of CD14+CD16- monocytes, which conversely produce a higher amount of IL-10. In addition, the CD4 +CD45RO+CD62L-/CD4+CD45RO +CD62L+ ratio was significantly lower after LCAP therapy. However, the CD4+CD25bright/total CD4+ ratio did not change. Conclusions: The present findings revealed the real target of proinflammatory CD14dullCD16+ monocytes removed during LCAP treatment of UC and that LCAP might be used as an extracorporeal anti-TNF-α therapy, expanding the clinical applications of this procedure to include the treatment of Crohn's disease.

Original languageEnglish
Pages (from-to)284-290
Number of pages7
JournalInflammatory bowel diseases
Volume13
Issue number3
DOIs
Publication statusPublished - 2007 Mar 1

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Keywords

  • CD14CD16 monocytes
  • Leukocytapheresis
  • Ulcerative colitis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Gastroenterology

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