Central role of interleukin-6 in burn induced stimulation of hepatic amino acid transport.
Burn injury produces a marked and prolonged hypermetabolic state, which is characterized by accelerated hepatic amino acid metabolism and negative nitrogen balance. The effect of burn injury on hepatocyte transport of glutamine, a key substrate in gluconeogenesis and ureagenesis, was examined following the administration of a full thickness 20% total body surface scald injury. The burn injury was induced in wild-type mice, as well as two types of knockout mice: a CD-14 knockout and an interleukin-6 (IL-6) knockout. In both the wild-type and CD-14 knockout mice a latent and profound 2-fold increase in hepatocyte glutamine transport was seen. In contrast, hepatocytes isolated from IL-6 knockout mice failed to show an induction of glutamine transport after burn injury. Hepatocytes isolated from burned wild-type and CD-14 knockout mice produced significantly higher levels of IL-6 as compared to hepatocytes isolated from sham burned mice. Histologic analysis of skin isolated from wild-type mice showed a robust inflammatory response whereas skin from IL-6 deficient mice showed minimal inflammation and decreased granulation tissue. The results of this study suggest that IL-6 may play a key role in the stimulation of hepatic glutamine transport following burn injury.
Pawlik
Timothy M
TM
Department of Surgical Oncology-444, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030-4009, USA. tmpawlik@mdanderson.org
Carter
Edward A
EA
Bode
Barry P
BP
Fischman
Alan J
AJ
Tompkins
Ronald G
RG
D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D002056:Burns / Q000473:pathology*; D005973:Glutamine / Q000737:chemistry; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology; D007249:Inflammation; D015850:Interleukin-6 / Q000235:genetics / Q000502:physiology*; D018950:Lipopolysaccharide Receptors / Q000235:genetics / Q000502:physiology*; D008070:Lipopolysaccharides / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological
D000596:Amino Acids; D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D005973:Glutamine