Jelkmann W E, Fandrey J, Frede S, Pagel H
Physiologisches Institut I, Universität Bonn, Germany.
Ann N Y Acad Sci. 1994 Apr 15;718:300-9; discussion 309-11.
In patients with the anemia of chronic diseases, the plasma level of EPO is often low in relation to the blood hemoglobin concentration. Because infectious and inflammatory processes cause activation of cytokine-producing macrophages and lymphocytes, we investigated whether isolated inflammatory cytokines influence the synthesis of EPO in vitro. IL-1 and TNF-alpha were shown to inhibit EPO mRNA levels and EPO formation in the human hepatoma cell cultures HepG2 and Hep3B, and to lower EPO formation in isolated perfused rat kidneys. IFN-alpha and IFN-beta also induced some inhibition of EPO production in HepG2 cultures. IL-3, TGF-beta 2, and IFN-gamma did not inhibit. IL-6 stimulated the production of EPO in Hep3B cells but was ineffective in HepG2 cells and lowered EPO production in isolated perfused rat kidneys. IL-1, TNF-alpha, and possibly other cytokines could contribute to defective EPO production in renal and nonrenal immune responses.
在患有慢性病贫血的患者中，促红细胞生成素（EPO）的血浆水平相对于血液血红蛋白浓度往往较低。由于感染和炎症过程会导致产生细胞因子的巨噬细胞和淋巴细胞被激活，我们研究了分离出的炎性细胞因子在体外是否会影响EPO的合成。白细胞介素-1（IL-1）和肿瘤坏死因子-α（TNF-α）在人肝癌细胞系HepG2和Hep3B培养物中可抑制EPO信使核糖核酸（mRNA）水平和EPO生成，并降低离体灌注大鼠肾脏中的EPO生成。α-干扰素（IFN-α）和β-干扰素（IFN-β）在HepG2培养物中也会对EPO产生一定抑制作用。白细胞介素-3（IL-3）、转化生长因子-β2（TGF-β2）和γ-干扰素（IFN-γ）则无抑制作用。白细胞介素-6（IL-6）可刺激Hep3B细胞中EPO的产生，但对HepG2细胞无效，且会降低离体灌注大鼠肾脏中的EPO产生。IL-1、TNF-α以及可能的其他细胞因子可能导致肾脏和非肾脏免疫反应中EPO产生缺陷。
