Role of IL-10 for induction of anemia during inflammation
Role of IL-10 for induction of anemia during inflammation
复制标题
DOI：
10.4049/jimmunol.169.4.2204
复制
发表时间：
2002-08-15
影响因子：
4.4
通讯作者：
Weiss, G
中科院分区：
文献类型：
--
作者：
Tilg, H;Ulmer, H;Weiss, G
患有慢性炎症性疾病的患者经常观察到贫血。最近的体外数据表明 Th2 细胞因子，例如 IL-10，可能参与其发病机制。作为一项随机、双盲、安慰剂对照研究的一部分，我们分析了 1) 329 名慢性活动性克罗恩病患者的血红蛋白值变化，这些患者接受抗炎细胞因子 IL-10，2) 这些患者亚组 (n = 54) 的血清铁参数，以及 3) 通过 Northern 印迹和免疫印迹法分析了 IL-10 对人单核细胞 (THP-1) 铁蛋白转录和翻译的体外影响。代谢标记后进行免疫沉淀。接受较高剂量 IL-10 的患者出现贫血，铁蛋白和可溶性转铁蛋白受体水平呈剂量依赖性增加，这是红系祖细胞铁限制的指标。根据我们的体外数据，高铁蛋白血症可能是由于活化的单核细胞中 IL-10 直接刺激铁蛋白翻译所致，最有可能是通过细胞因子介导的翻译抑制蛋白（铁调节蛋白）与铁蛋白 mRNA 5'-非翻译区的结合亲和力降低所致。在患者中，所有观察到的变化在治疗结束时（+29 天）最为明显，此后血红蛋白水平和血清铁参数在随访 4 周内恢复到基线水平。我们的数据表明，IL-10 会导致炎症性肠病患者贫血，这可能与细胞因子诱导铁稳态失衡有关，导致高铁蛋白血症和红系祖细胞铁利用率有限，这是慢性炎症性贫血中常见的情况。
Anemia is frequently observed in patients suffering from chronic inflammatory disorders. Recent in vitro data suggest that Th2 cytokines, such as IL-10, could be involved in its pathogenesis. We analyzed 1) changes in hemoglobin values in 329 patients with chronic active Crohn's disease receiving the anti-inflammatory cytokine IL-10 as part of a randomized, double-blind, placebo-controlled study, 2) serum iron parameters in a subgroup of these patients (n = 54), and 3) the in vitro effects of IL-10 on ferritin transcription and translation in human monocytic cells (THP-1) by means of Northern blot and immunoprecipitation after metabolic labeling. Patients receiving higher doses of IL-10 developed anemia and presented with a dose-dependent increase of ferritin and soluble transferrin receptor levels, an indicator of iron restriction to erythroid progenitor cells. According to our in vitro data, hyperferritinemia may result from direct stimulation of ferritin translation by IL-10 in activated monocytic cells, most likely by cytokine-mediated reduction of the binding affinity of translational repressors, iron-regulatory proteins, to the 5'-untranslated region of ferritin mRNA. In patients, all observed changes were most pronounced at the end of therapy (day +29), and thereafter hemoglobin levels and serum iron parameters returned to baseline levels within 4 wk of follow-up. Our data demonstrate that IL-10 causes anemia in patients with inflammatory bowel disease which may be referred to the induction of imbalances in iron homeostasis by the cytokine, leading to hyperferritinemia and limited iron availability to erythroid progenitor cells, a condition typically seen in the anemia of chronic inflammation.