Impaired febrile responses of aging mice are mediated by endogenous lipocortin-1 (annexin-1).
The mechanisms underlying age-related impairments in febrile responses were investigated in female C57Bl/lcrf-a(t) mice. Injection of norepinephrine, to assess total thermogenic capacity, significantly increased oxygen consumption (VO2) in all age groups, although the responses of the aged mice were significantly reduced. Injection of lipopolysaccharide or murine interleukin-1 beta (mIL-1 beta) significantly increased body temperature and VO2 in the young and adult mice but not in the aged mice. The impaired responses to mIL-1 beta in the aged mice were normalized by either injection of the glucocorticoid receptor antagonist RU-38486 or by injection of an antiserum to lipocortin-1 or its purified immunoglobulin G fraction. Injection of prostaglandin E2 significantly increased VO2 and body temperature in all age groups. Resting plasma corticosterone concentrations were significantly elevated in the aged and adult mice, whereas injection of mIL-1 beta significantly raised plasma corticosterone concentrations in all animals. These findings indicate that the impaired febrile response of aged female C57Bl/lcrf-a(t) mice may be caused by increased concentrations and/or sensitivity to endogenous glucocorticoids. The impaired febrile responses of aged mice appear to be mediated by endogenous lipocortin-1.
Strijbos
P J
PJ
Department of Physiological Sciences, University of Manchester, United Kingdom.
Horan
M A
MA
Carey
F
F
Rothwell
N J
NJ
D000375:Aging / Q000502:physiology*; D000818:Animals; D017305:Annexin A1 / Q000276:immunology / Q000502:physiology*; D001831:Body Temperature / Q000187:drug effects; D003345:Corticosterone / Q000097:blood; D015232:Dinoprostone / Q000494:pharmacology; D005260:Female; D005334:Fever / Q000097:blood / Q000503:physiopathology*; D007106:Immune Sera / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007375:Interleukin-1 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D015735:Mifepristone / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D009994:Osmolar Concentration; D010101:Oxygen Consumption / Q000187:drug effects
D017305:Annexin A1; D007106:Immune Sera; D007074:Immunoglobulin G; D007375:Interleukin-1; D008070:Lipopolysaccharides; D015735:Mifepristone; D015232:Dinoprostone; D003345:Corticosterone; D009638:Norepinephrine