炎症性肠病患者中促炎CD14+CD16+DR++单核细胞的吸附性清除
Adsorptive depletion of elevated proinflammatory CD14+CD16+DR++ monocytes in patients with inflammatory bowel disease.
作者信息
Hanai Hiroyuki, Iida Takayuki, Takeuchi Ken, Watanabe Fumitoshi, Yamada Masami, Kikuyama Masataka, Maruyama Yasushi, Iwaoka Yasushi, Hirayama Kazuhisa, Nagata Seiji, Takai Kenji
机构信息
Centre for Gastroenterology and Inflammatory Bowel Disease Research, Hamamatsu South Hospital, Hamamatsu, Japan.
出版信息
Am J Gastroenterol. 2008 May;103(5):1210-6. doi: 10.1111/j.1572-0241.2007.01714.x. Epub 2008 Jan 2.
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.
背景
在人体血液中，存在两种单核细胞群体，即CD14(++)CD16(-)经典单核细胞和CD14(+)CD16(+)促炎单核细胞，后者约占单核细胞总数的10%，但在炎症状态下会增多。CD14(+)CD16(+)单核细胞可产生大量炎性细胞因子，包括肿瘤坏死因子-α（TNF-α）和白细胞介素-1（IL-1）。吸附柱吸附载体可从血液中吸附大部分单核细胞/巨噬细胞和粒细胞，这与活动性炎症性肠病（IBD）患者的临床疗效相关。本研究旨在调查IBD患者中CD14(+)CD16(+)单核细胞的情况以及吸附柱对这种促炎表型的影响。
方法
本研究共纳入58例溃疡性结肠炎（UC，n = 37）或克罗恩病（CD，n = 21）患者以及11名健康对照者。采用三色免疫荧光和流式细胞术检测外周血CD14(+)CD16(+)单核细胞。
结果
活动性CD患者中CD14(+)CD16(+)单核细胞的百分比显著高于对照组（P = 0.0089），也高于静止期CD患者（P = 0.0419）和静止期UC患者（P = 0.0063）。此外，正在服用泼尼松龙（PSL）的活动性UC患者中CD14(+)CD16(+)单核细胞的百分比低于未服用PSL的患者（P < 0.0001），因此PSL可能对CD14(+)CD16(+)单核细胞有抑制作用。活动性IBD患者在8周内均接受了最多10次吸附柱粒细胞/单核细胞吸附（GMA）治疗。与治疗前水平相比，CD14(+)CD16(+)单核细胞的百分比显著下降（UC患者中P = 0.0077，CD患者中P = 0.0117）。
结论
通过GMA显著降低外周血CD14(+)CD16(+)单核细胞应可减轻炎症驱动，并有助于该治疗方法的临床疗效。皮质类固醇也可使CD14(+)CD16(+)单核细胞减少。因此，皮质类固醇应可增强GMA的疗效。这是关于IBD患者经吸附柱GMA治疗后CD14(+)CD16(+)单核细胞减少的首篇报道。
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