Service de Médecine Interne, Hôpital Européen Georges Pompidou, 75908 Paris Cedex 15, France.
Pediatrics. 2010 Dec;126(6):e1608-12. doi: 10.1542/peds.2010-1123. Epub 2010 Nov 1.
In addition to occasional autoimmune hemolytic anemia, unexplained iron-deficiency anemia has been reported in childhood Castleman disease (CD). The recent discovery of hepcidin has regenerated the research on iron metabolism. This hormone is a key regulator of iron homeostasis, mainly by inhibiting intestinal iron absorption. Liver expression of hepcidin increases in response to interleukin 6 (IL-6). With chronic overproduction of IL-6 as a hallmark, CD could be an interesting human model for studying the contribution of the IL-6/hepcidin pathway in the pathogenesis of anemia of chronic disease. We report here the case of a 16-year-old boy with chronic iron-deficiency anemia (plasma ferritin: 19 μg/L; plasma iron: 2.2 μmol/L; negative bone marrow Perls' Prussian blue stain), inflammatory syndrome (C-reactive protein: 108 mg/L), and growth retardation for the previous 2 years. Diagnostic workup revealed a large mesenteric mass corresponding to localized CD of mixed histologic type. Resection of the tumor resulted in complete resolution of iron-deficiency anemia and inflammatory syndrome. Parallel variations of plasma IL-6, C-reactive protein, and hepcidin concentrations, together with tumor immunohistochemistry, strongly suggested that IL-6 synthesized by the tumor caused both the inflammation and iron deficiency through enhancement of hepcidin production by the liver. The results of this unique case study (1) explain the mechanism of iron deficiency observed in some children with CD, (2) confirm in vivo the regulatory effect of IL-6 in human hepcidin production, and (3) suggest that iron deficiency is a causal link between IL-6 and anemia of chronic disease.
除了偶尔发生的自身免疫性溶血性贫血外，儿童期 Castleman 病（CD）也会出现原因不明的缺铁性贫血。新近发现的铁调素使人们对铁代谢的研究重新活跃起来。这种激素是铁稳态的主要调节因子，主要通过抑制肠道铁吸收来实现。肝铁调素的表达会随着白细胞介素 6（IL-6）的增加而增加。CD 的特征是慢性过度产生 IL-6，因此它可能是研究 IL-6/铁调素途径在慢性病性贫血发病机制中的作用的一个有趣的人类模型。我们在此报告 1 例 16 岁男孩，患有慢性缺铁性贫血（血浆铁蛋白：19μg/L；血浆铁：2.2μmol/L；骨髓 Perls'普鲁士蓝染色阴性）、炎症综合征（C 反应蛋白：108mg/L）和 2 年来生长迟缓。诊断性检查发现，一个大的肠系膜肿块对应于局灶性混合组织学类型的 CD。肿瘤切除导致缺铁性贫血和炎症综合征完全缓解。血浆 IL-6、C 反应蛋白和铁调素浓度的平行变化，以及肿瘤免疫组化，强烈提示肿瘤合成的 IL-6 通过增强肝脏铁调素的产生，导致了炎症和缺铁。这项独特的病例研究的结果（1）解释了一些 CD 患儿中观察到的缺铁机制，（2）在体内证实了 IL-6 对人类铁调素产生的调节作用，（3）提示缺铁是 IL-6 和慢性病性贫血之间的因果关系。
