Diminished acute phase response and increased hepatic inflammation of aged rats in response to intraperitoneal injection of lipopolysaccharide.
Aging is associated with a deterioration of the acute phase response to inflammatory challenges. However, the nature of these defects remains poorly defined. We analyzed the hepatic inflammatory response after intraperitoneal administration of lipopolysaccharide (LPS) given to Fisher 344 rats aged 6, 15, and 22-23 months. Induction of the acute phase proteins (APPs), haptoglobin, alpha-1-acid glycoprotein, and T-kininogen was reduced and/or retarded with aging. Initial induction of interleukin-6 in aged rats was normal, but the later response was increased relative to younger counterparts. An exacerbated hepatic injury was observed in aged rats receiving LPS, as evidenced by the presence of multiple microabscesses in portal tracts, confluent necrosis, higher neutrophil accumulation, and elevated serum levels of alanine aminotransferase, relative to younger animals. Our results suggest that aged rats displayed a reduced expression of APPs and increased hepatic injury in response to the inflammatory insult.
Gomez
Christian R
CR
National Institute on Aging, NIA/NIH, Bethesda MD 20892, USA.
Acuña-Castillo
Claudio
C
Pérez
Claudio
C
Leiva-Salcedo
Elías
E
Riquelme
Denise M
DM
Ordenes
Gamaliel
G
Oshima
Kiyoko
K
Aravena
Mauricio
M
Pérez
Viviana I
VI
Nishimura
Sumiyo
S
Sabaj
Valeria
V
Walter
Robin
R
Sierra
Felipe
F
D000209:Acute-Phase Proteins / Q000378:metabolism*; D000375:Aging / Q000276:immunology*; D000818:Animals; D006520:Hepatitis, Animal / Q000276:immunology*; D007150:Immunohistochemistry; D007274:Injections, Intraperitoneal; D015850:Interleukin-6 / Q000097:blood; D008070:Lipopolysaccharides / Q000009:adverse effects; D008099:Liver / Q000378:metabolism; D008297:Male; D009504:Neutrophils; D051381:Rats; D011916:Rats, Inbred F344
D000209:Acute-Phase Proteins; D015850:Interleukin-6; D008070:Lipopolysaccharides