慢性病贫血患儿肿瘤坏死因子α、白介素6与红细胞生成素的关系

Relationship between tumor necrosis factor alpha,interleukin-6 and erythropoietin in children′s with chronic anemia and influence of recombinant human tumor necrosis factor alpha on erythropoietin gene expression

目的 探讨小儿慢性病贫血 (ACD)血清红细胞生成素 (EPO)水平与肿瘤坏死因子α(TNF α)、白介素 6 (IL 6 )的关系以及体外重组TNF α(rhTNF α)对EPO产生的影响。方法 住院患儿6 0例 ,其中ACD组 2 0例 ,慢性病无贫血组 (NA) 19例 ,缺铁性贫血组 (IDA) 2 1例。TNF α、IL 6采用ELISA方法检测 ,EPO应用化学发光法测定 ,对人肝癌细胞株HepG2进行体外培养 ,应用逆转录 聚合酶链反应 (RT PCR)半定量方法 ,探讨rhTNF α对EPO生成的影响。结果 三组患儿血清EPO水平差异有显著性 (F =4 4 6 8,P <0 0 1) ,ACD患儿血清EPO水平高于NA患儿 ,但在相同Hb值时 ,ACD患儿EPO低于IDA患儿。三组患儿血清TNF α水平差异有显著性 (F =2 5 12 ,P <0 0 1) ,血清TNF α水平 ,ACD组高于NA组和IDA组 ;三组患儿血清IL 6水平差异有显著性 (F =13 2 6 ,P <0 0 1) ,血清IL 6水平ACD组高于NA组和IDA组。ACD患儿血清TNF α及血清IL 6与EPO无相关性 (r=- 0 35 ,P >0 0 5 ;r=- 0 0 5 ,P >0 0 5 )。体外实验中 ,rhTNF α抑制低氧状态下EPOmRNA的表达 ,且随着rhTNF α剂量的增大而对EPO抑制作用增强 (F =6 4 2 0 ,P <0 0 1)。结论 ACD患儿EPO虽存在代偿性增高但代偿生成不足 ,是小儿ACD的发病原因之一 ;血清TNF α、IL

Objective The anemia of chronic disease (ACD) is usually defined as mild to moderate anemia occurring during the chronic infection, inflammation, neoplasm or trauma It is the most common anemia among in hospital adults The insufficient endogenous erythropoietin (EPO) production is probably one of the pathogenic mechanisms of ACD Inflammatory cytokines play an important role in the ACD pathogenesis But nowadays there are few published papers on the childhood ACD in the world This study aimed to detect the EPO levels in children′s ACD, to explore the relationship between EPO and tumor necrosis factor α(TNFα) and interleukin 6 (IL 6) and, to evaluate the effect of recombinant human TNFα(rhTNF α) on EPO gene expression Methods Sixty children were divided into ACD group (20 children), non anemia (NA) group (19 children) and iron deficiency anemia(IDA) group (21 children) according to clinical diagnosis Serum TNF α and IL 6 levels were detected with ELISA method The EPO level was detected by chemical immulite method The effect of rhTNF α on the expression of EPO gene was studied by culturing Hep G2 cell line and RT PCR method Results Serum EPO levels were different among the 3 groups ( F =44 68, P <0 01) Serum EPO levels in ACD group were higher than those in NA group, while the hemoglobin levels were similar between the two groups Serum EPO levels in ACD patients were lower than those in IDA patients Serum TNFα levels were different among the 3 groups ( F =25 15, P <0 01), and serum IL 6 levels were also different among the 3 groups ( F =13 16, P <0 01) Serum TNFα and IL 6 levels in ACD group were higher than those in NA group In ACD group, serum levels of both TNFα and IL 6 were not correlated to the serum level of EPO ( r =-0 35, P >0 05 and r =-0 05, P >0 05, respectively) In vitro, rhTNFα inhibited the expression of EPO mRNA in hypoxia, and the inhibitory effects became stronger with the increase of rhTNFα ( F =64 20, P <0 01) Conclusion EPO levels increased incompensatively in ACD children, which may be a cause of ACD TNFα may cause anemia by inhibiting EPO production.