Yasushi Iwaoka

Adsorptive Granulocyte and Monocyte Apheresis versus Prednisolone in Patients with Corticosteroid-Dependent Moderately Severe Ulcerative Colitis

Background/Aim: Active ulcerative colitis (UC) is often associated with increased peripheral granulocytes and monocytes/macrophages which show activation behavior and prolonged survival time. Further, mucosal granulocyte level parallels intestinal inflammation and can predict UC relapse. Accordingly, our aim was to see if adsorptive granulocyte/monocyte apheresis (GMA) can promote remission and spare steroid in patients with steroid-dependent (SD) UC. Methods: 69 SD patients, at the time of relapse, were randomly assigned to groups I (n = 46) and II (n = 23). The mean dose of prednisolone (PSL) was 12 mg/day/patient, CAI (clinical activity index) 9.2 in both groups. Group I patients were given up to 11 GMA sessions over 10 weeks with Adacolumn; in group II, the mean dose of PSL was increased to 30 mg/day/patient. Results: At week 12, 83% of group I and 65% of group II patients were in remission, CAI in group I was 1.7 (p < 0.001) and in group II, 2.5 (p < 0.001). Further, during the 12 weeks of treatment, the cumulative amount of PSL received per patient was 1,157 mg in group I and 1,938 mg in group II (p = 0.001). Conclusions: GMA appeared to be an effective adjunct to standard drug therapy of moderately severe UC by promoting remission and sparing steroids.

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-α 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 Crohns 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.

Correlation of Serum Soluble TNF-|[alpha]| Receptors I and II Levels with Disease Activity in Patients with Ulcerative Colitis

OBJECTIVES:TNF-α has a major role in inflammatory bowel disease via two receptors, p55 (RI) and p75 (RII) expressed on many cell types, in particular neutrophils and monocytes (GM). Upon activation of these leukocytes, RI and RII are shed into the medium and can neutralize TNF. Accordingly, soluble RI and RII (s-RI/RII) are believed to have potent antiinflammatory actions. Further, in active UC, GM are elevated with activation behavior and recently adsorptive GM apheresis (GMA) in patients with severe UC was associated with a dramatic efficacy. In this study, we investigated the effects of GMA on serum s-RI/RII.METHODS:Thirty-one patients with UC, clinical activity index (CAI) 11.1 were treated with GMA by using the Adacolumn. In the column, leukocytes which bear the FcγR and complement receptors adhere to the column apheresis carriers (neutrophils, monocytes, and a small fraction of lymphocytes). One GMA session was 60 min at 30 mL/min and each patient could receive up to 11 sessions over 8 wk. Serum s-RI/II were measured in the blood at the column inflow (peripheral blood, time 0 and 60 min) and outflow at 60 min.RESULTS:Serum s-RI/RII showed strong correlation with CAI, r = 0.849 (p < 0.001) and r = 0.867 (p < 0.001), respectively and were greater than when patients were in remission or the levels in controls (p < 0.001). s-RI/RII at the column outflow were higher compared with inflow (p < 0.05) suggesting that RI/RII were shed from leukocytes which adhere to the carriers. Similarly s-RI/RII were significantly increased in the peripheral blood at the end of the 60 min GMA session compared with time 0. After 11 GMA sessions, CAI fell to remission level in 26 of 31 patients accompanied by falls of s-RI/RII.CONCLUSIONS:The sources of s-RI/RII are believed to be activated monocytes and neutrophils with further release when these leukocytes adhere to the column carriers. s-RI/RII released during GMA should contribute to the clinical efficacy of this procedure.