Comparison of the effects of aging and IL-6 on the hepatic inflammatory response in two models of systemic injury: scald injury versus i.p. LPS administration.
Regardless of age, a marked elevation in circulating IL-6 levels correlates with increased mortality after injury or an inflammatory challenge. We previously reported that aged IL-6 knockout mice given LPS have improved survival and reduced inflammatory response than LPS-treated aged wild type (WT) mice. Herein, we analyzed the effects of aging and IL-6 on the hepatic inflammatory response in two models of systemic injury: dorsal scald (burn) injury versus intraperitoneal LPS administration. At 24 h after burn injury, circulating alanine aminotransferase and hepatic neutrophil accumulation were comparable regardless of age or IL-6 deficiency. However, at this same time point, these indicators of liver damage, in addition to hepatic levels of KC, a neutrophil chemoattractant, were increased in aged WT mice given LPS relative to young WT mice given LPS. The hepatic injury was drastically reduced in aged IL-6 knockout mice given LPS as compared with LPS-exposed aged WT mice. Our results suggest that the nature of the insult will determine the degree of remote injury in aged animals. In addition, the role of IL-6 as a contributing factor of tissue injury may be insult specific.
Gomez
Christian R
CR
The Burn and Shock Trauma Institute, Department of Surgery, and Immunology and Aging Program, Loyola University Medical Center, Maywood, IL 60153, USA.
Nomellini
Vanessa
V
Baila
Horea
H
Oshima
Kiyoko
K
Kovacs
Elizabeth J
EJ
D000375:Aging; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D002056:Burns / Q000378:metabolism*; D005260:Female; D007249:Inflammation / Q000097:blood* / Q000473:pathology; D015850:Interleukin-6 / Q000097:blood* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000008:administration & dosage* / Q000633:toxicity; D008099:Liver / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D016896:Treatment Outcome
D015850:Interleukin-6; D008070:Lipopolysaccharides; D009195:Peroxidase; D000410:Alanine Transaminase