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Adsorptive depletion of elevated proinflammatory CD14+CD16+DR++ monocytes in patients with inflammatory bowel disease
Hiroyuki Hanai1, Takayuki Iida, Ken Takeuchi
1Centre for Gastroenterology and Inflammatory Bowel Disease Research, Hamamatsu South Hospital, Hamamatsu, Japan.
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.
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