The anemia of inflammation is related in part to abnormal erythropoiesis in bone marrow. G-CSF regulates granulopoiesis and is increased during systemic inflammation. Here, we have showed that high levels of G-CSF are associated with repression of bone marrow erythropoiesis and expansion of splenic erythropoiesis in Escherichia coli-infected mice and lipopolysaccharide-treated mice. Under lipopolysaccharide-induced systemic inflammatory conditions in mice, G-CSF neutralization with antibody alleviated the blockage of bone marrow erythropoiesis, prevented the enhancement of splenic erythropoiesis, ameliorated splenomegaly, and reduced the brittleness of spleen. We further demonstrated that after lipopolysaccharide treatment, TLR4-knockout mice display low levels of G-CSF, healthy bone marrow erythropoiesis, almost no stress erythropoiesis in the spleen, and normal size and toughness of spleen. In addition, we found HIF-mediated erythropoietin production is essential for splenic erythropoiesis in the setting of G-CSF-induced suppression of bone marrow erythropoiesis. Our findings identify G-CSF as a critical mediator of inflammation-associated erythropoiesis dysfunction in bone marrow and offer insight into the mechanism of G-CSF-induced splenic erythropoiesis. We provide experimentally significant dimension to the biology of G-CSF.

中文翻译：

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在全身炎症的情况下，G-CSF 将红细胞生成从骨髓转移到脾脏。

炎症性贫血部分与骨髓中的异常红细胞生成有关。G-CSF 调节粒细胞生成并在全身炎症期间增加。在这里，我们已经表明高水平的 G-CSF 与抑制骨髓红细胞生成和脾红细胞生成在大肠杆菌感染的小鼠和脂多糖处理的小鼠中的扩张有关。在脂多糖诱导的小鼠全身炎症条件下，G-CSF抗体中和可减轻骨髓红细胞生成的阻塞，阻止脾红细胞生成的增强，改善脾肿大，减轻脾的脆性。我们进一步证明，脂多糖处理后，TLR4基因敲除小鼠的 G-CSF 水平低，骨髓红细胞生成健康，脾脏中几乎没有应激性红细胞生成，脾脏大小和韧性正常。此外，我们发现在 G-CSF 诱导的骨髓红细胞生成抑制的情况下，HIF 介导的红细胞生成素的产生对于脾红细胞生成是必不可少的。我们的研究结果将 G-CSF 确定为骨髓中炎症相关红细胞生成功能障碍的关键介质，并提供对 G-CSF 诱导的脾红细胞生成机制的深入了解。我们为 G-CSF 的生物学提供了具有实验意义的维度。