Huang Q H, Hruby V J, Tatro J B
Division of Endocrinology, Diabetes, Metabolism and Molecular Medicine, Department of Medicine and the Tupper Research Institute, Tufts University School of Medicine and New England Medical Center Hospitals, Boston, Massachusetts 02111, USA.
Am J Physiol. 1999 Mar;276(3):R864-71. doi: 10.1152/ajpregu.1999.276.3.R864.
Inflammation and microbial infection produce symptoms, including fever, anorexia, and hypoactivity, that are thought to be mediated by endogenous proinflammatory cytokines. Melanocortins are known to act centrally to suppress effects on fever and other sequelae of proinflammatory cytokine actions in the central nervous system, but the roles of melanocortins in anorexia and hypoactivity occurring during the acute phase response are unknown. The present study was designed to determine the effects of exogenous and endogenous alpha-melanocyte stimulating hormone (alpha-MSH) on lipopolysaccharide (LPS)-induced anorexia in relation to their effects on fever. Rats were fasted overnight to promote feeding behavior, then injected intraperitoneally with LPS (100 micrograms/kg ip), followed 30 min later by intracerebroventricular injection of either alpha-MSH or the melanocortin receptor subtype 3/subtype 4 (MC3-R/MC4-R) antagonist SHU-9119. Food intake, locomotor activity, and body temperature (Tb) were monitored during the ensuing 24-h period. Each of two intracerebroventricular doses of alpha-MSH (30 and 300 ng) potentiated the suppressive effects of LPS on food intake and locomotion, despite the fact that the higher dose alleviated LPS-induced fever. In control rats that were not treated with LPS, only the higher dose of alpha-MSH significantly inhibited food intake, and Tb and locomotor activity were unaffected. To assess the roles of endogenous central melanocortins, LPS-treated rats received intracerebroventricular SHU-9119 (200 ng). Central MC3-R/MC4-R blockade did not affect Tb or food intake in the absence of LPS treatment, but it reversed the LPS-induced reduction in 24-h food intake and increased LPS-induced fever without altering the LPS-induced suppression of locomotion. Taken together, the results suggest that exogenous and endogenous melanocortins acting centrally exert divergent influences on different aspects of the acute phase response, suppressing LPS-induced fever but contributing to LPS-induced anorexia and hypoactivity.
炎症和微生物感染会产生包括发热、厌食和活动减退在内的症状，这些症状被认为是由内源性促炎细胞因子介导的。已知促黑素在中枢发挥作用，以抑制对发热及中枢神经系统中促炎细胞因子作用的其他后遗症的影响，但促黑素在急性期反应期间出现的厌食和活动减退中的作用尚不清楚。本研究旨在确定外源性和内源性α-黑素细胞刺激素（α-MSH）对脂多糖（LPS）诱导的厌食的影响及其与对发热的影响的关系。大鼠禁食过夜以促进进食行为，然后腹腔注射LPS（100微克/千克腹腔注射），30分钟后脑室内注射α-MSH或促黑素受体亚型3/亚型4（MC3-R/MC4-R）拮抗剂SHU-9119。在随后的24小时内监测食物摄入量、运动活动和体温（Tb）。尽管较高剂量的α-MSH可减轻LPS诱导的发热，但脑室内两种剂量的α-MSH（30和300纳克）均增强了LPS对食物摄入和运动的抑制作用。在未用LPS处理的对照大鼠中，只有较高剂量的α-MSH显著抑制食物摄入，而Tb和运动活动未受影响。为了评估内源性中枢促黑素的作用，用LPS处理的大鼠接受脑室内注射SHU-9119（200纳克）。在未进行LPS处理时，中枢MC3-R/MC4-R阻断不影响Tb或食物摄入，但它逆转了LPS诱导的24小时食物摄入量减少，并增加了LPS诱导的发热，而不改变LPS诱导的运动抑制。综上所述，结果表明，中枢作用的外源性和内源性促黑素对急性期反应的不同方面产生不同影响，抑制LPS诱导的发热，但导致LPS诱导的厌食和活动减退。
