Strijbos P J, Horan M A, Carey F, Rothwell N J
Department of Physiological Sciences, University of Manchester, United Kingdom.
Am J Physiol. 1993 Aug;265(2 Pt 1):E289-97. doi: 10.1152/ajpendo.1993.265.2.E289.
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.
在雌性C57Bl/lcrf-a(t)小鼠中研究了发热反应中与年龄相关的损伤机制。注射去甲肾上腺素以评估总产热能力，所有年龄组的耗氧量（VO2）均显著增加，尽管老年小鼠的反应明显减弱。注射脂多糖或小鼠白细胞介素-1β（mIL-1β）可显著提高年轻和成年小鼠的体温和VO2，但对老年小鼠无效。通过注射糖皮质激素受体拮抗剂RU-38486或注射抗脂皮质素-1抗血清或其纯化的免疫球蛋白G组分，可使老年小鼠对mIL-1β的受损反应恢复正常。注射前列腺素E2可显著提高所有年龄组的VO2和体温。老年和成年小鼠的静息血浆皮质酮浓度显著升高，而注射mIL-1β可显著提高所有动物的血浆皮质酮浓度。这些发现表明，老年雌性C57Bl/lcrf-a(t)小鼠发热反应受损可能是由于对内源性糖皮质激素的浓度增加和/或敏感性增加所致。老年小鼠发热反应受损似乎是由内源性脂皮质素-1介导的。
