Adsorptive depletion of elevated proinflammatory CD14+CD16+DR++ monocytes in patients with inflammatory bowel disease

Am J Gastroenterol. 2008 May;103(5):1210-6. doi: 10.1111/j.1572-0241.2007.01714.x. Epub 2008 Jan 2.

Abstract

Background: In human blood, two monocyte populations exist, CD14(++)CD16(-) classical monocytes and CD14(+)CD16(+) proinflammatory monocytes, which account for about 10% of total monocytes, but can expand to promote inflammatory conditions. CD14(+)CD16(+) monocytes produce large amounts of inflammatory cytokines including TNF-alpha and IL-1. Adacolumn adsorptive carriers adsorb from the blood in the column most of the monocytes/macrophages and granulocytes and this has been associated with clinical efficacy in patients with active inflammatory bowel disease (IBD). This study was to investigate the CD14(+)CD16(+) monocyte profile in patients with IBD and the impact of Adacolumn on this proinflammatory phenotype.

Methods: A total of 58 patients with ulcerative colitis (UC, N = 37) or Crohn's disease (CD, N = 21) together with 11 healthy controls were included in this study. Peripheral blood CD14(+)CD16(+) monocytes were determined by three-color immunofluorescence and flow cytometry.

Results: The percentage of CD14(+)CD16(+) monocytes in patients with active CD was significantly (P= 0.0089) higher than the level in the control group, in patients with quiescent CD (P= 0.0419) or quiescent UC (P= 0.0063). Further, the percentage of CD14(+)CD16(+) monocytes in patients with active UC who were on prednisolone (PSL) was less than the level in those not on PSL (P < 0.0001), thus PSL might have a suppressive effect on CD14(+)CD16(+) monocytes. Patients with active IBD were each given up to 10 Adacolumn granulocye/monocyte adsorption (GMA) sessions over an 8-wk period. The percentage of CD14(+)CD16(+) monocytes decreased dramatically (P= 0.0077 in UC and P= 0.0117 in CD) compared with entry levels.

Conclusions: A significant reduction in peripheral CD14(+)CD16(+) monocytes by GMA should mitigate the inflammatory drive and contribute to the clinical efficacy of this procedure. Reduction of CD14(+)CD16(+) monocytes by corticosteroids was also seen. Hence, corticosteroids should enhance the efficacy of GMA. This is the first report on CD14(+)CD16(+) monocytes being decreased by Adacolumn GMA in patients with IBD.

MeSH terms

  • Adolescent
  • Adult
  • Antigens, CD / blood*
  • Colitis, Ulcerative / immunology
  • Colitis, Ulcerative / therapy*
  • Crohn Disease / immunology
  • Crohn Disease / therapy*
  • Drug Therapy, Combination
  • Female
  • Flow Cytometry
  • GPI-Linked Proteins
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Leukapheresis*
  • Leukocyte Count
  • Leukocytes, Mononuclear / immunology*
  • Lipopolysaccharide Receptors / blood*
  • Male
  • Mesalamine / therapeutic use
  • Middle Aged
  • Prednisolone / therapeutic use
  • Receptors, IgG / blood*
  • Treatment Outcome

Substances

  • Antigens, CD
  • FCGR3B protein, human
  • GPI-Linked Proteins
  • Immunosuppressive Agents
  • Lipopolysaccharide Receptors
  • Receptors, IgG
  • Mesalamine
  • Prednisolone