Intrahepatic STAT-3 activation and acute phase gene expression predict outcome after CLP sepsis in the rat

被引:66
作者
Andrejko, KM [1 ]
Chen, JD [1 ]
Deutschman, CS [1 ]
机构
[1] Univ Penn, Sch Med, Dept Anesthesia, Philadelphia, PA 19104 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY | 1998年 / 275卷 / 06期
关键词
cytokines; tumor necrosis factor-alpha; mortality; multiple organ dysfunction syndrome; systemic inflammatory response syndrome; alpha(2)-macroglobulin;
D O I
10.1152/ajpgi.1998.275.6.G1423
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
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 alpha(2)-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 C-LP. 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.
引用
收藏
页码:G1423 / G1429
页数:7
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