Adsorptive depletion of elevated proinflammatory CD14+CD16+DR++ monocytes in patients with inflammatory bowel disease.
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.
Hanai
Hiroyuki
H
Centre for Gastroenterology and Inflammatory Bowel Disease Research, Hamamatsu South Hospital, Hamamatsu, Japan.
Iida
Takayuki
T
Takeuchi
Ken
K
Watanabe
Fumitoshi
F
Yamada
Masami
M
Kikuyama
Masataka
M
Maruyama
Yasushi
Y
Iwaoka
Yasushi
Y
Hirayama
Kazuhisa
K
Nagata
Seiji
S
Takai
Kenji
K
D000293:Adolescent; D000328:Adult; D015703:Antigens, CD / Q000097:blood*; D003093:Colitis, Ulcerative / Q000276:immunology / Q000628:therapy*; D003424:Crohn Disease / Q000276:immunology / Q000628:therapy*; D004359:Drug Therapy, Combination; D005260:Female; D005434:Flow Cytometry; D058851:GPI-Linked Proteins; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007937:Leukapheresis; D007958:Leukocyte Count; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D018950:Lipopolysaccharide Receptors / Q000097:blood*; D008297:Male; D019804:Mesalamine / Q000627:therapeutic use; D008875:Middle Aged; D011239:Prednisolone / Q000627:therapeutic use; D017452:Receptors, IgG / Q000097:blood*; D016896:Treatment Outcome
D015703:Antigens, CD; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D007166:Immunosuppressive Agents; D018950:Lipopolysaccharide Receptors; D017452:Receptors, IgG; D019804:Mesalamine; D011239:Prednisolone