Schreiber S, Fedorak R N, Nielsen O H, Wild G, Williams C N, Nikolaus S, Jacyna M, Lashner B A, Gangl A, Rutgeerts P, Isaacs K, van Deventer S J, Koningsberger J C, Cohard M, LeBeaut A, Hanauer S B
Charité University Hospital, Fourth Medical Department, Humboldt University, Berlin, Germany.
Gastroenterology. 2000 Dec;119(6):1461-72. doi: 10.1053/gast.2000.20196.
BACKGROUND & AIMS: Interleukin (IL)-10 is a cytokine with potent anti-inflammatory properties. We investigated the safety and efficacy of different doses of human recombinant (rhu)IL-10 in patients with Crohn's disease (CD).
A prospective, multicenter, double-blind, placebo-controlled study was conducted in 329 therapy-refractory patients with CD. Clinical improvement was defined by a reduction of the Crohn's Disease Activity Index (CDAI) by 100 points or more and clinical remission by a decrease of the CDAI to <150 points. At selected centers, patients underwent ileocolonoscopies and activation of the nuclear factor-kappa B (NF-kappa B) system was assessed in biopsy specimens.
Subcutaneous treatment with rhuIL-10 over 28 days induced a fully reversible, dose-dependent decrease in hemoglobin and thrombocyte counts but no clinically significant side effects. No differences in the induction of remission were observed between rhuIL-10 groups (1 microg, 18% [9.6-29.2]; 4 microg, 20% [11.3-32.2]; 8 microg, 20% [11.1-31.8]; 20 microg, 28% [18-40.7]; and placebo, 18% [9.6-29.6]). Clinical improvement was observed in 46% (33.7-59) in the 8-microg/kg rhuIL-10 group in comparison with 27% (17-39.6) in patients taking placebo. Responders to rhuIL-10 showed inhibition of NF-kappaB p65 activation in contrast to nonresponders.
Up to 8 microg/kg of rhuIL-10 was well tolerated. A tendency toward clinical improvement but not remission was observed in the 8-microg/kg dose group. Further studies should delineate which subgroups of patients with CD benefit from rhuIL-10 therapy.
白细胞介素（IL）-10是一种具有强大抗炎特性的细胞因子。我们研究了不同剂量的重组人（rhu）IL-10对克罗恩病（CD）患者的安全性和疗效。
对329例难治性CD患者进行了一项前瞻性、多中心、双盲、安慰剂对照研究。临床改善定义为克罗恩病活动指数（CDAI）降低100分或更多，临床缓解定义为CDAI降至<150分。在选定的中心，患者接受了回结肠镜检查，并在活检标本中评估了核因子-κB（NF-κB）系统的激活情况。
28天的rhuIL-10皮下治疗导致血红蛋白和血小板计数出现完全可逆的剂量依赖性下降，但无临床显著副作用。rhuIL-10组（1微克，18%[9.6-29.2]；4微克，20%[11.3-32.2]；8微克，20%[11.1-31.8]；20微克，28%[18-40.7]）与安慰剂组（18%[9.6-29.6]）在诱导缓解方面未观察到差异。与安慰剂组相比，8微克/千克rhuIL-10组有46%（33.7-59）的患者出现临床改善，而服用安慰剂的患者为27%（17-39.6）。与无反应者相比，rhuIL-10反应者显示NF-κB p65激活受到抑制。
高达8微克/千克的rhuIL-10耐受性良好。8微克/千克剂量组观察到有临床改善的趋势，但未出现缓解。进一步研究应明确哪些CD患者亚组能从rhuIL-10治疗中获益。
