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 norepi nephrine, to assess total thermogenic capacity, significantly increase d oxygen consumption (VO2) in all age groups, although the responses o f the aged mice were significantly reduced. Injection of lipopolysacch aride or murine interleukin-1beta (mIL-1beta) significantly increased body temperature and VO2 in the young and adult mice but not in the ag ed mice. The impaired responses to mIL-1beta in the aged mice were nor malized by either injection of the glucocorticoid receptor antagonist RU-38486 or by injection of an antiserum to lipocortin-1 or its purifi ed immunoglobulin G fraction. Injection of prostaglandin E2 significan tly increased VO2 and body temperature in all age groups. Resting plas ma corticosterone concentrations were significantly elevated in the ag ed and adult mice, whereas injection of mIL-1beta significantly raised plasma corticosterone concentrations in all animals. These findings i ndicate 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.