Central nervous system inflammation induces muscle atrophy via activation of the hypothalamic-pituitary-adrenal axis.
Central nervous system inflammation induces muscle atrophy via activation of the hypothalamic-pituitary-adrenal axis.
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DOI：
10.1084/jem.20111020
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发表时间：
2011-11-21
期刊：
影响因子：
--
通讯作者：
Marks DL
中科院分区：
文献类型：
--
作者：
Braun TP;Zhu X;Szumowski M;Scott GD;Grossberg AJ;Levasseur PR;Graham K;Khan S;Damaraju S;Colmers WF;Baracos VE;Marks DL
全身性和CNS界定的炎症以依赖于糖皮质激素信号传导的方式触发骨骼肌catalysts。骨骼肌松解症是许多慢性疾病的共病，是全身炎症的结果。虽然直接的炎症细胞因子作用于肌肉促进萎缩，非肌肉部位的炎症介质的行动很少被描述。我们证明，中枢神经系统（CNS）界定的白细胞介素1β（IL-1β）信号传导单独可以引起肌肉中的分解代谢程序，迅速诱导萎缩。这种效应依赖于下丘脑-垂体-肾上腺（HPA）轴激活，因为CNS IL-1β诱导的萎缩可通过肾上腺切除术消除。此外，我们确定了一个糖皮质激素反应基因的表达模式保守的急性和慢性炎症性肌肉萎缩模型。与研究表明炎症细胞因子对肌肉的直接作用足以诱导catastrophic相反，肾上腺切除术还阻断了响应全身炎症的萎缩程序，表明糖皮质激素是该过程所必需的。此外，与炎症条件下产生的糖皮质激素相当的循环水平足以引起严重的肌肉萎缩。总之，这些数据表明，炎症诱导的肌肉紧张症的一个重要组成部分间接通过中枢神经系统中的中继发生。
Systemic and CNS-delimited inflammation triggers skeletal muscle catabolism in a manner dependent on glucocorticoid signaling. Skeletal muscle catabolism is a co-morbidity of many chronic diseases and is the result of systemic inflammation. Although direct inflammatory cytokine action on muscle promotes atrophy, nonmuscle sites of action for inflammatory mediators are less well described. We demonstrate that central nervous system (CNS)–delimited interleukin 1β (IL-1β) signaling alone can evoke a catabolic program in muscle, rapidly inducing atrophy. This effect is dependent on hypothalamic–pituitary–adrenal (HPA) axis activation, as CNS IL-1β–induced atrophy is abrogated by adrenalectomy. Furthermore, we identified a glucocorticoid-responsive gene expression pattern conserved in models of acute and chronic inflammatory muscle atrophy. In contrast with studies suggesting that the direct action of inflammatory cytokines on muscle is sufficient to induce catabolism, adrenalectomy also blocks the atrophy program in response to systemic inflammation, demonstrating that glucocorticoids are requisite for this process. Additionally, circulating levels of glucocorticoids equivalent to those produced under inflammatory conditions are sufficient to cause profound muscle wasting. Together, these data suggest that a significant component of inflammation-induced muscle catabolism occurs indirectly via a relay in the CNS.
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