Wang Wen, Zhang Mao-Hong, Yu Yuan, Xu Cong-gao
Department of Hematology, Qilu Hospital of Shandong University, Jinan 250012, China.
Zhonghua Xue Ye Xue Za Zhi. 2007 Oct;28(10):681-4.
To explore impaired erythropoiesis and relative inadequacy of erythropoietin production in the anemic cancer patients and the correlation of tumor necrosis factor-alpha (TNF-alpha) or interferon-gamma (IFN-gamma) with inadequate erythropoietin (EPO) response and impaired erythropoiesis in cancer patients with anemia.
Fifty adult anemic and 15 non-anemic tumor patients were studied. Serum EPO levels were measured by radioimmunoassay (RIA) and serum soluble transferrin receptor (sTfR). TNF-alpha and IFN-gamma levels by enzyme-linked immunosorbent assay (ELISA). Log transformed EPO and sTfR values were used in statistical analysis. The R correlation analyses were performed.
The mean serum immunoreactive erythropoietin level in anemic cancer patients [(23.11 +/- 10.00) IU/L] was not significantly higher than in healthy people (P = 0.053), but significantly lower than in IDA patients with similar degree of anemia [(43.00 +/- 22.00) IU/L, P < 0.01]. Both O/P EPO [0.88 (0.54-1.10)] and O/P sTfR [0.89 (0.57-1.22)] were significantly lower in anemic cancer patients than in controls and in non-anemic cancer patients. There was no significant difference between the latter two groups. Furthermore, the expected inverse linear relation between serum EPO and hemoglobin levels was absent in the anemic cancer patients, and so did the relation between serum sTfR and hemoglobin levels. There was no correlation between O/P EPO and O/P sTfR. The serum levels of both TNF-alpha and IFN-gamma in anemic cancer patients [(25.75 +/- 26.71) ng/L, (50.49 +/- 42.12) ng/L, respectively] were significantly higher than those in healthy controls (both P < 0.01) or in nonanemic cancer patients (both 0.01 < P < 0.05), and so did between non-anemic cancer patients and controls. The serum levels of TNF-alpha were inversely correlated with hemoglobin levels (r = - 0.40, P = 0.004), O/P EPO (r = -0.32, P = 0.025) or O/P sTfR (r = -0.36, P = 0.01); while serum levels of IFN-gamma were inversely correlated with hemoglobin levels (r = -0.36, P = 0.01) or O/P sTfR (r = 0.39, P = 0.006), but not with O/P EPO. Conclusions Anemia of cancer is due to impaired erythropoiesis and relative inadequacy of EPO production. TNF-alpha might inhibit EPO production and erythropoiesis, while IFN-gamma maybe directly inhibit erythropoiesis and be independent of EPO response inadequacy.
探讨贫血癌症患者红细胞生成受损及促红细胞生成素产生相对不足的情况，以及肿瘤坏死因子-α（TNF-α）或干扰素-γ（IFN-γ）与贫血癌症患者促红细胞生成素（EPO）反应不足及红细胞生成受损之间的相关性。
对50例成年贫血肿瘤患者和15例非贫血肿瘤患者进行研究。采用放射免疫分析法（RIA）测定血清EPO水平，采用酶联免疫吸附测定法（ELISA）测定血清可溶性转铁蛋白受体（sTfR）、TNF-α和IFN-γ水平。统计分析采用对数转换后的EPO和sTfR值，并进行R相关性分析。
贫血癌症患者血清免疫反应性促红细胞生成素平均水平[（23.11±10.00）IU/L]虽不显著高于健康人（P = 0.053），但显著低于程度相似的缺铁性贫血（IDA）患者[（43.00±22.00）IU/L，P < 0.01]。贫血癌症患者的O/P EPO[0.88（0.54 - 1.10）]和O/P sTfR[0.89（0.57 - 1.22）]均显著低于对照组和非贫血癌症患者。后两组之间无显著差异。此外，贫血癌症患者血清EPO与血红蛋白水平之间不存在预期的负线性关系，血清sTfR与血红蛋白水平之间也不存在这种关系。O/P EPO与O/P sTfR之间无相关性。贫血癌症患者血清TNF-α和IFN-γ水平[分别为（25.75±26.71）ng/L，（50.49±42.12）ng/L]显著高于健康对照组（均P < 0.01）或非贫血癌症患者（均0.01 < P < 0.05），非贫血癌症患者与对照组之间也是如此。血清TNF-α水平与血红蛋白水平呈负相关（r = - 0.40，P = 0.004）、与O/P EPO呈负相关（r = -0.32，P = 0.025）或与O/P sTfR呈负相关（r = -0.36，P = 0.01）；而血清IFN-γ水平与血红蛋白水平呈负相关（r = -0.36，P = 0.01）或与O/P sTfR呈负相关（r = 0.39，P = 0.006），但与O/P EPO无相关性。结论癌症贫血是由于红细胞生成受损和EPO产生相对不足所致。TNF-α可能抑制EPO产生和红细胞生成，而IFN-γ可能直接抑制红细胞生成且与EPO反应不足无关。
