Insights into the role of interleukin-6 in the induction of hepatic injury after trauma-hemorrhagic shock.
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 approximately 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 B(2) (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 A(2) 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 A(2) levels.
Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, AL 35294-0019, USA.
Balazs
B
Toth
Yukihiro
Y
Yokoyama
Martin G
MG
Schwacha
Richard L
RL
George
Loring W
LW
Rue
Kirby I
KI
Bland
Irshad H
IH
Chaudry
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D015850:Interleukin-6 / Q000097:blood*; D008102:Liver Circulation / Q000502:physiology; D008107:Liver Diseases / Q000209:etiology* / Q000378:metabolism*; D008297:Male; D017082:Portal Pressure / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000150:complications* / Q000378:metabolism*; D013929:Thromboxane B2 / Q000097:blood; D000093242:Interleukin-6 Inhibitors
D000410:Alanine Transaminase; D015850:Interleukin-6; D013929:Thromboxane B2; D000093242:Interleukin-6 Inhibitors