Central nervous system inflammation induces muscle atrophy via activation of the hypothalamic-pituitary-adrenal axis

Theodore P. Braun, Xinxia Zhu, Marek Szumowski, Gregory D. Scott, Aaron Grossberg, Peter R. Levasseur, Kathryn Graham, Sheehan Khan, Sambasivarao Damaraju, William F. Colmers, Vickie E. Baracos, Daniel Marks

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

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 glucocorticoidresponsive 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 inflammationinduced muscle catabolism occurs indirectly via a relay in the CNS.

Original languageEnglish (US)
Pages (from-to)2449-2463
Number of pages15
JournalJournal of Experimental Medicine
Volume208
Issue number12
DOIs
StatePublished - Nov 21 2011

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Muscular Atrophy
Central Nervous System
Inflammation
Atrophy
Muscles
Adrenalectomy
Interleukin-1
Glucocorticoids
Cytokines
Skeletal Muscle
Chronic Disease
Morbidity
Gene Expression

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Central nervous system inflammation induces muscle atrophy via activation of the hypothalamic-pituitary-adrenal axis. / Braun, Theodore P.; Zhu, Xinxia; Szumowski, Marek; Scott, Gregory D.; Grossberg, Aaron; Levasseur, Peter R.; Graham, Kathryn; Khan, Sheehan; Damaraju, Sambasivarao; Colmers, William F.; Baracos, Vickie E.; Marks, Daniel.

In: Journal of Experimental Medicine, Vol. 208, No. 12, 21.11.2011, p. 2449-2463.

Research output: Contribution to journalArticle

Braun, TP, Zhu, X, Szumowski, M, Scott, GD, Grossberg, A, Levasseur, PR, Graham, K, Khan, S, Damaraju, S, Colmers, WF, Baracos, VE & Marks, D 2011, 'Central nervous system inflammation induces muscle atrophy via activation of the hypothalamic-pituitary-adrenal axis', Journal of Experimental Medicine, vol. 208, no. 12, pp. 2449-2463. https://doi.org/10.1084/jem.20111020
Braun, Theodore P. ; Zhu, Xinxia ; Szumowski, Marek ; Scott, Gregory D. ; Grossberg, Aaron ; Levasseur, Peter R. ; Graham, Kathryn ; Khan, Sheehan ; Damaraju, Sambasivarao ; Colmers, William F. ; Baracos, Vickie E. ; Marks, Daniel. / Central nervous system inflammation induces muscle atrophy via activation of the hypothalamic-pituitary-adrenal axis. In: Journal of Experimental Medicine. 2011 ; Vol. 208, No. 12. pp. 2449-2463.
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