[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].
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 alpha (TNF alpha) and interleukin-6 (IL-6) and, to evaluate the effect of recombinant human TNF alpha (rhTNF-alpha) 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 alpha and IL-6 levels were detected with ELISA method. The EPO level was detected by chemical immulite method. The effect of rhTNF alpha 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 TNF alpha 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 TNF alpha and IL-6 levels in ACD group were higher than those in NA group. In ACD group, serum levels of both TNF alpha 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, rhTNF alpha inhibited the expression of EPO mRNA in hypoxia, and the inhibitory effects became stronger with the increase of rhTNF alpha (F = 64.20, P < 0.01).


CONCLUSIONS
EPO levels increased incompensatively in ACD children, which may be a cause of ACD. TNF alpha may cause anemia by inhibiting EPO production.
Department of Internal Medicine, Children's Hospital of Fudan University, Shanghai 200032, China.
Xiao-wen
XW
Zhai
Yue
Y
Wu
Xiao-feng
XF
Gu
Feng-juan
FJ
Lu
D000740:Anemia / Q000097:blood / Q000235:genetics*; D045744:Cell Line, Tumor / Q000187:drug effects / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D004921:Erythropoietin / Q000097:blood / Q000235:genetics*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology
D015850:Interleukin-6; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D004921:Erythropoietin