Frede S, Fandrey J, Pagel H, Hellwig T, Jelkmann W
Institute of Physiology, University of Bonn, Germany.
Am J Physiol. 1997 Sep;273(3 Pt 2):R1067-71. doi: 10.1152/ajpregu.1997.273.3.R1067.
Proinflammatory cytokines play an important role in the pathogenesis of anemia in inflammatory diseases. Interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) have been reported to inhibit the synthesis of erythropoietin (EPO) in vitro. To evaluate the in vivo significance of this observation, we have investigated effects of the administration of bacterial lipopolysaccharide (LPS) and IL-1 beta on renal EPO production in rats. Measurements by competitive reverse-transcription polymerase chain reaction showed that EPO mRNA levels were significantly reduced in the kidneys of normoxic rats 6 h after the injection of LPS (0.1 or 1 mg/kg). In addition, LPS and IL-1 beta (1 microgram/kg) inhibited the increase in EPO mRNA and plasma EPO levels when administered to rats before hypoxia exposure (8% O2 in the inspiratory gas). Evidence for an inflammatory reaction in the kidneys of LPS-treated rats was provided by measurements of greatly elevated renal TNF-alpha mRNA levels. Furthermore, kidneys isolated from LPS-created rats produced less immunoreactive EPO when perfused hypoxically in vitro for 2 h. Thus mediators of the immune response inhibit renal EPO gene expression in vivo, which is relevant with respect to the impaired synthesis of EPO in inflammatory diseases in humans.
促炎细胞因子在炎症性疾病所致贫血的发病机制中起重要作用。据报道，白细胞介素-1（IL-1）和肿瘤坏死因子-α（TNF-α）在体外可抑制促红细胞生成素（EPO）的合成。为评估这一观察结果在体内的意义，我们研究了给予细菌脂多糖（LPS）和IL-1β对大鼠肾脏EPO生成的影响。通过竞争性逆转录聚合酶链反应测量发现，注射LPS（0.1或1mg/kg）6小时后，常氧大鼠肾脏中的EPO mRNA水平显著降低。此外，在低氧暴露（吸入气体中含8% O2）前给大鼠注射LPS和IL-1β（1μg/kg）可抑制EPO mRNA和血浆EPO水平的升高。通过测量LPS处理大鼠肾脏中显著升高的TNF-α mRNA水平，为其肾脏炎症反应提供了证据。此外，从LPS处理大鼠分离出的肾脏在体外低氧灌注2小时后产生的免疫反应性EPO较少。因此，免疫反应介质在体内可抑制肾脏EPO基因表达，这与人类炎症性疾病中EPO合成受损有关。
