Insights into the role of interleukin-6 in the induction of hepatic injury after trauma-hemorrhagic shock

Balazs Toth, Yukihiro Yokoyama, Martin G. Schwacha, Richard L. George, Loring W. Rue, Kirby I. Bland, Irshad H. Chaudry

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

Although systemic interleukin-6 (IL-6) level is elevated, hepatocellular function is impaired and liver injury occurs after trauma-hemorrhage (T-H), it remains unknown whether a causal relationship exists between elevated IL-6 levels and liver injury after T-H. We hypothesized that IL-6 is causative in the development of hepatic dysfunction and injury after T-H. To examine this, adult male Sprague-Dawley rats underwent a 5-cm midline laparotomy and were subjected to hemorrhagic shock (blood pressure = 35 mmHg for ∼90 min), followed by resuscitation (Ringer lactate, 4 times the shed blood volume). At 2, 5, and 24 h thereafter, blood samples were collected and the liver isolated and perfused for 60 min. Portal inflow pressure was measured, and perfusate samples were collected to measure IL-6, alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) levels. A significant positive correlation between plasma levels of IL-6 and ALT and perfusate levels of IL-6 and LDH levels was observed. In a second series of experiments, rats were treated with immunoglobulin G (IgG) or antibodies against rat IL-6 (anti-IL-6) at the onset of resuscitation. At 5 h after resuscitation, anti-IL-6 treatment attenuated the T-H induced increases in plasma ALT and thromboxane B2 (a thromboxane A 2 metabolite) levels, and bile flow was normalized to sham levels. Perfusion of livers from normal rats with IL-6 did not alter portal pressure; however, perfusion of a stable thromboxane A2 analog dose dependently increased portal pressure. Thus IL-6 plays a significant role in the induction of hepatic dysfunction and liver injury after T-H that appears to be in part mediated by increased thromboxane A2 levels.

Original languageEnglish (US)
Pages (from-to)2184-2189
Number of pages6
JournalJournal of applied physiology
Volume97
Issue number6
DOIs
StatePublished - Dec 1 2004
Externally publishedYes

Keywords

  • Cytokine
  • Hemorrhage
  • Isolated liver perfusion
  • Lactate dehydrogenase
  • Liver

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Fingerprint Dive into the research topics of 'Insights into the role of interleukin-6 in the induction of hepatic injury after trauma-hemorrhagic shock'. Together they form a unique fingerprint.

  • Cite this