Tsantes Argirios, Bonovas Stefanos, Tassiopoulos Stergios, Filioussi Kalitsa, Vlachou Athina, Meletis John, Papadhimitriou Stefanos, Vaiopoulos George
Laboratory of Haematology, G. Gennimatas General Hospital of Athens, Athens, Greece.
Med Sci Monit. 2005 Apr;11(4):CR177-81. Epub 2005 Mar 24.
Despite the severe derangement of gas exchange in the advanced stages of idiopathic pulmonary fibrosis (IPF), secondary erythrocytosis is either absent or much lower than is seen in chronic obstructive pulmonary disease (COPD) with comparable hypoxemia. This study investigates the differences in erythropoiesis between IPF and COPD, searching for the possible underlying mechanisms.
MATERIAL/METHODS: The study included 32 patients with COPD, 18 patients with IPF, all with overt hypoxemia (PO(2) <65 mmHg), and 34 healthy controls. Erythrocytic parameters and serum erythropoietin (EPO) levels were assessed for all subjects. In a number of patients from both groups, the development of erythroid colonies grown from peripheral blood mononuclear cells was assayed in semisolid methylcellulose cultures and compared to cultures of control cells, in the presence of patient or control serum.
Hb and serum EPO levels were significantly higher in the COPD group than in IPF patients and controls. However, the number of BFU-E colonies obtained from mononuclear cells of IPF patients was clearly higher than in COPD patients when the same culture medium was used. Unlike COPD sera, IPF sera induced a significant growth inhibition of erythroid bursts arising from mononuclear cells of both patients and controls.
Our findings suggest a kind of ineffective erythropoiesis in IPF. Defective EPO production and inhibitory effect on erythropoiesis exerted by pro-inflammatory cytokines released from alveolar macrophages may be implicated in the suboptimal erythropoietic response. However, the possible involvement of other factors affecting erythropoiesis in IPF requires further investigation.
尽管特发性肺纤维化（IPF）晚期存在严重的气体交换紊乱，但继发性红细胞增多症要么不存在，要么比具有类似低氧血症的慢性阻塞性肺疾病（COPD）患者低得多。本研究调查IPF和COPD之间红细胞生成的差异，寻找可能的潜在机制。
材料/方法：该研究纳入了32例COPD患者、18例IPF患者，所有患者均有明显低氧血症（PO₂<65 mmHg），以及34名健康对照者。评估了所有受试者的红细胞参数和血清促红细胞生成素（EPO）水平。在两组的一些患者中，在半固体甲基纤维素培养物中检测了外周血单个核细胞生成的红系集落的发育情况，并在患者或对照血清存在的情况下与对照细胞培养物进行比较。
COPD组的血红蛋白（Hb）和血清EPO水平显著高于IPF患者和对照组。然而，当使用相同培养基时，从IPF患者单个核细胞获得的爆式红系集落形成单位（BFU-E）集落数量明显高于COPD患者。与COPD血清不同，IPF血清对患者和对照组单个核细胞产生的红系爆式集落有显著的生长抑制作用。
我们的研究结果提示IPF存在一种无效的红细胞生成。促红细胞生成素产生缺陷以及肺泡巨噬细胞释放的促炎细胞因子对红细胞生成的抑制作用可能与次优的红细胞生成反应有关。然而，IPF中其他影响红细胞生成的因素的可能参与情况需要进一步研究。
