title: Aberrant acute-phase response in aged interleukin-6 knockout mice.
abstract: 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.
authors.affiliation: 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.
authors.forename: Christian R
authors.initials: CR
authors.lastname: Gomez
authors.forename: Joanna
authors.initials: J
authors.lastname: Goral
authors.forename: Luis
authors.initials: L
authors.lastname: Ramirez
authors.forename: Manfred
authors.initials: M
authors.lastname: Kopf
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Kovacs
mesh_terms: 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
chemical_list: D000209:Acute-Phase Proteins; D002352:Carrier Proteins; D015850:Interleukin-6; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D000685:Serum Amyloid A Protein; D000099231:Lipopolysaccharide-Binding Protein