Aberrant acute-phase response in aged interleukin-6 knockout mice.
This study was designed to determine whether the acute-phase response in aged mice is altered by interleukin (IL) 6 deficiency. Young and aged wild-type (WT) and IL-6 knockout (KO) BALB/C female mice were injected with lipopolysaccharide (LPS; 1.5 microg/g body weight). After 24 h, aged IL-6 KO mice had an improved survival when compared with aged WT mice. Serum levels of IL-6 in aged WT animals given LPS were determined and, as expected, were significantly higher when compared with young LPS-treated WT animals (P<0.05). Serum levels of the acute-phase protein, serum amyloid A, were 50% lower in aged LPS-treated IL-6 KO mice relative to aged WT mice given LPS (P<0.001). In contrast, the induction of LPS-binding protein was not affected by age or IL-6 deficiency in LPS-treated animals. Circulating levels of corticosterone were markedly reduced in aged LPS-treated IL-6 KO mice relative to aged WT mice given LPS. These data indicate that IL-6 is an important contributor to the outcome of the acute-phase response of aged individuals challenged with endotoxin. We conclude that the absence of IL-6, a cytokine that contributes to the elevated basal proinflammatory state observed in aging, can improve the ability of aged mice to withstand an otherwise lethal challenge of bacterial endotoxin.
Gomez
Christian R
CR
Department of Cell Biology, Neurobiology, and Anatomy, The Burn and Shock Trauma Institute, Alcohol Research Program, and Immunology and Aging Program, Loyola University Medical Center, Maywood, IL 60130, USA.
Goral
Joanna
J
Ramirez
Luis
L
Kopf
Manfred
M
Kovacs
Elizabeth J
EJ
D000209:Acute-Phase Proteins; D000210:Acute-Phase Reaction / Q000097:blood* / Q000139:chemically induced; D000375:Aging / Q000097:blood*; D000818:Animals; D002352:Carrier Proteins / Q000097:blood*; D005260:Female; D015850:Interleukin-6 / Q000172:deficiency*; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000633:toxicity*; D008562:Membrane Glycoproteins / Q000097:blood*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D000685:Serum Amyloid A Protein / Q000032:analysis*; D000099231:Lipopolysaccharide-Binding Protein
D000209:Acute-Phase Proteins; D002352:Carrier Proteins; D015850:Interleukin-6; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D000685:Serum Amyloid A Protein; D000099231:Lipopolysaccharide-Binding Protein