Andrejko K M, Chen J, Deutschman C S
Department of Anesthesia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-4283, USA.
Am J Physiol. 1998 Dec;275(6):G1423-9. doi: 10.1152/ajpgi.1998.275.6.G1423.
Interleukin-6 (IL-6) regulates hepatic acute phase responses by activating the transcription factor signal transducer and activator of transcription (STAT)-3. IL-6 also may modulate septic pathophysiology. We hypothesize that 1) STAT-3 activation and transcription of alpha2-macroglobulin (A2M) correlate with recovery from sepsis and 2) STAT-3 activation and A2M transcription reflect intrahepatic and not serum IL-6. Nonlethal sepsis was induced in rats by single puncture cecal ligation and puncture (CLP) and lethal sepsis via double-puncture CLP. STAT-3 activation and A2M transcription were detected at 3-72 h and intrahepatic IL-6 at 24-72 h following single-puncture CLP. All were detected only at 3-16 h following double-puncture CLP and at lower levels than following single-puncture CLP. Loss of serum and intrahepatic IL-6 activity after double-puncture CLP correlated with mortality. Neither intrahepatic nor serum IL-6 levels correlated with intrahepatic IL-6 activity. STAT-3 activation following single-puncture CLP inversely correlated with altered transcription of gluconeogenic, ketogenic, and ureagenic genes. IL-6 may have both beneficial and detrimental effects in sepsis. Fulminant sepsis may decrease the ability of hepatocytes to respond to IL-6.
白细胞介素-6（IL-6）通过激活转录因子信号转导子和转录激活子（STAT）-3来调节肝脏急性期反应。IL-6也可能调节脓毒症的病理生理过程。我们假设：1）STAT-3激活及α2-巨球蛋白（A2M）转录与脓毒症恢复相关；2）STAT-3激活及A2M转录反映的是肝内IL-6而非血清IL-6。通过单次盲肠结扎和穿刺（CLP）诱导大鼠发生非致死性脓毒症，通过双次穿刺CLP诱导大鼠发生致死性脓毒症。在单次穿刺CLP后3 - 72小时检测STAT-3激活及A2M转录，在24 - 72小时检测肝内IL-6。在双次穿刺CLP后仅在3 - 16小时检测到所有这些指标，且水平低于单次穿刺CLP后。双次穿刺CLP后血清和肝内IL-6活性丧失与死亡率相关。肝内和血清IL-6水平均与肝内IL-6活性无关。单次穿刺CLP后STAT-3激活与糖异生、生酮和尿素生成基因转录改变呈负相关。IL-6在脓毒症中可能具有有益和有害两种作用。暴发性脓毒症可能会降低肝细胞对IL-6的反应能力。
