In vivo suppression of erythropoiesis by tumor necrosis factor-alpha (TNF-alpha): reversal with exogenous erythropoietin (EPO).
In vivo suppression of erythropoiesis by tumor necrosis factor-alpha (TNF-alpha): reversal with exogenous erythropoietin (EPO).
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DOI：
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发表时间：
1990-02
影响因子：
2.6
通讯作者：
C. Johnson;Cookingham Ca;P. Furmanski
中科院分区：
文献类型：
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作者：
C. Johnson;Cookingham Ca;P. Furmanski
肿瘤坏死因子- α (tnf - α)在体外和体内选择性地杀死肿瘤细胞，作为一种癌症治疗剂正在进行试验。我们已经证明，tnf - α显著抑制晚期红细胞生成，导致慢性治疗小鼠贫血。这些促红细胞生成作用可能限制tnf - α的临床应用。因此，我们研究了促红细胞生成素（EPO）是否可以用于预防tnf - α诱导的红细胞抑制。正常小鼠分别接受单剂量重组小鼠tnf - α （10(5) U/小鼠，i.p）和不同浓度的重组人EPO。3天后，通过测定脾脏和骨髓中成熟红细胞集落形成细胞（CFU-E）的数量来观察对晚期红细胞生成的影响。与EPO同时治疗以剂量依赖的方式消除了tnf - α的抑制作用。EPO治疗还可以防止外周血红细胞压积的下降，这是在慢性（5 × 10(4) U/小鼠/天，连续5天）给予tnf - α时观察到的。EPO治疗不影响tnf - α诱导的肿瘤出血性坏死和巨噬细胞（CFU-M）祖细胞的刺激。这些结果表明，同时注射促红细胞生成素可以消除tnf α诱导的红细胞生成抑制作用。
Tumor necrosis factor-alpha (TNF-alpha) selectively kills tumor cells in vitro and in vivo and is being tested as a cancer therapeutic agent. We have shown that TNF-alpha significantly suppresses late-stage erythropoiesis, leading to anemia in chronically treated mice. These erythropoietic effects could limit the clinical use of TNF-alpha. Therefore, we have examined whether erythropoietin (EPO) could be used to prevent TNF-alpha-induced erythroid suppression. Normal mice were treated with a single dose of recombinant murine TNF-alpha (10(5) U/mouse, i.p.) with and without various concentrations of recombinant human EPO. After 3 days, effects on late-stage erythropoiesis were measured by determining the number of mature erythroid colony-forming cells (CFU-E) in the spleen and bone marrow. Simultaneous treatment with EPO abrogated the suppressive effect of TNF-alpha in a dose-dependent manner. EPO treatment also prevented the decrease in peripheral blood-hematocrit that was observed with chronic (5 x 10(4) U/mouse/day for 5 days) administration of TNF-alpha. TNF-alpha-induced hemorrhagic necrosis of tumors and stimulation of macrophage (CFU-M) progenitors were unaffected by EPO treatment. These results demonstrate that simultaneous injection of EPO can abrogate the TNF-alpha-induced suppressive effects on erythropoiesis.