TY - JOUR
T1 - Insights into the role of interleukin-6 in the induction of hepatic injury after trauma-hemorrhagic shock
AU - Toth, Balazs
AU - Yokoyama, Yukihiro
AU - Schwacha, Martin G.
AU - George, Richard L.
AU - Rue, Loring W.
AU - Bland, Kirby I.
AU - Chaudry, Irshad H.
PY - 2004/12
Y1 - 2004/12
N2 - 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.
AB - 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.
KW - Cytokine
KW - Hemorrhage
KW - Isolated liver perfusion
KW - Lactate dehydrogenase
KW - Liver
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U2 - 10.1152/japplphysiol.00499.2004
DO - 10.1152/japplphysiol.00499.2004
M3 - Article
C2 - 15298985
AN - SCOPUS:9244231803
VL - 97
SP - 2184
EP - 2189
JO - Journal of Applied Physiology
JF - Journal of Applied Physiology
SN - 0161-7567
IS - 6
ER -