Casadevall N
Laboratoire d'Hématologie, Hôpital Raymond Poincaré, Garches, France.
Nephrol Dial Transplant. 1995;10 Suppl 6:27-30. doi: 10.1093/ndt/10.supp6.27.
Erythropoiesis is controlled by different regulators. Interleukin 3, granulocyte-macrophage colony-stimulating factor and stem cell factor play regulatory functions in the early steps of erythropoiesis. Erythropoietin (Epo) is the main factor which acts positively on the last steps of the production of erythrocytes in mammals. Epo is specific for the erythroid progenitor cells and has only little effect on other cells. The target cells for Epo are the erythroid progenitors (BFUe and CFUe). Epo acts on these progenitors through surface receptors specific for Epo. Epo induces the proliferation and differentiation of erythroid progenitors leading finally to reticulocytes. During this process, certain conditions are required to permit this differentiation: progenitors must be present in sufficient numbers, the bone marrow environment must be normal, and nutrients such as folic acid, vitamin B12 and particularly iron must be available. Elemental iron is an absolute requirement for adequate haemoglobin formation. Indeed, in a normal adult, without any stimulation, the bone marrow synthesizes 4 x 10(14) molecules of haemoglobin per second, each molecule containing four atoms of iron, which roughly corresponds to 20 mg iron. On the other hand, erythropoiesis is negatively regulated by several cytokines. These are macrophage-derived cytokines, including tumour necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), interleukin-6 (IL-6) and transforming growth factor-beta (TGF-beta). All these factors are elevated in the inflammatory state and are implicated in the pathogenesis of anaemia of chronic disease. TNF-alpha has an inhibitory effect on erythroid progenitors either directly or mediated by interferon-beta (INF-beta). IL-1 inhibits erythropoiesis in vivo in mice and in vitro in humans.(ABSTRACT TRUNCATED AT 250 WORDS)
红细胞生成受多种调节因子控制。白细胞介素3、粒细胞-巨噬细胞集落刺激因子和干细胞因子在红细胞生成的早期阶段发挥调节作用。促红细胞生成素（Epo）是对哺乳动物红细胞生成最后阶段起正向作用的主要因子。Epo对红系祖细胞具有特异性，对其他细胞影响很小。Epo的靶细胞是红系祖细胞（爆式红系集落形成单位和红系集落形成单位）。Epo通过Epo特异性表面受体作用于这些祖细胞。Epo诱导红系祖细胞增殖和分化，最终形成网织红细胞。在此过程中，需要某些条件来促进这种分化：祖细胞数量必须充足，骨髓环境必须正常，并且必须有叶酸、维生素B12尤其是铁等营养物质。元素铁是形成足够血红蛋白的绝对必需物质。事实上，在正常成年人中，在没有任何刺激的情况下，骨髓每秒合成4×10¹⁴个血红蛋白分子，每个分子含有四个铁原子，这大致相当于20毫克铁。另一方面，红细胞生成受到多种细胞因子的负调节。这些是巨噬细胞衍生的细胞因子，包括肿瘤坏死因子-α（TNF-α）、白细胞介素-1（IL-1）、白细胞介素-6（IL-6）和转化生长因子-β（TGF-β）。所有这些因子在炎症状态下都会升高，并与慢性病贫血的发病机制有关。TNF-α对红系祖细胞有直接或由干扰素-β（INF-β）介导的抑制作用。IL-1在小鼠体内和人体体外抑制红细胞生成。（摘要截断于250字）
