Document Detail


Beta-adrenergic blockade exacerbates sepsis-induced changes in tumor necrosis factor alpha and interleukin-6 in skeletal muscle and is associated with impaired translation initiation.
MedLine Citation:
PMID:  18301218     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Sepsis stimulates the sympathetic nervous system. The resultant elevation in plasma catecholamines, both norepinephrine and epinephrine (Epi), might be expected to alter the expression of inflammatory cytokines, which may directly or indirectly influence muscle protein balance. The purpose of this study was twofold: (1) determine whether Epi per se increases cytokine expression in skeletal muscle, and (2) determine whether beta-adrenergic blockade alters the sepsis-induced expression of inflammatory cytokines and mediators of protein balance in skeletal muscle.
METHODS: In the first study, rats were infused with Epi for 2 hour to increase the circulating Epi concentration to levels seen in septic animals. In the second study, sepsis was induced by cecal ligation and puncture and a nonspecific beta-adrenergic blockade produced with a continuous infusion of propranolol (PP). Tissues were obtained 24 after induction of sepsis and analyzed for tumor necrosis factor (TNF)-alpha interleukin (IL)-1beta, IL-6 mRNA and protein content. In addition, the tissue content of insulin-like growth factor (IGF)-I and various regulators of protein synthesis were assessed.
RESULTS: Epi acutely increased TNF-alpha IL-6 and IL-1beta mRNA content in muscle (3- to 40-fold). However, only the TNF-alpha and IL-6 protein content was increased in muscle by Epi. In the second study, beta-adrenergic blockade with PP exacerbated the sepsis-induced increase in muscle IL-6 and TNF-alpha mRNA but did not alter the increment in IL-1beta or HMGB1. Propranolol also accentuated the sepsis-induced increase in both IL-6 and TNF-alpha protein in muscle. The exaggerated muscle cytokine response in septic rats treated with PP was associated with a reduction in muscle IGF-I protein that was greater than detected in saline-infused septic rats. Finally, the combination of sepsis + PP also accentuated the sepsis-induced decrease in the phosphorylation of 4E-binding protein-1, ribosomal protein S6, and mTOR, which are key proteins controlling protein synthesis.
CONCLUSIONS: These results demonstrate that although Epi is capable of increasing tissue cytokines in naive rats, inhibition of the beta-adrenergic effects of catecholamines exacerbates the sepsis-induced increase of selected inflammatory cytokines. This exaggerated tissue response is associated with alterations in muscle IGF-I protein and translation initiation, which would be expected to impair tissue protein synthesis.
Authors:
Charles H Lang; Gerald Nystrom; Robert A Frost
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  The Journal of trauma     Volume:  64     ISSN:  1529-8809     ISO Abbreviation:  J Trauma     Publication Date:  2008 Feb 
Date Detail:
Created Date:  2008-02-27     Completed Date:  2008-03-07     Revised Date:  2014-09-16    
Medline Journal Info:
Nlm Unique ID:  0376373     Medline TA:  J Trauma     Country:  United States    
Other Details:
Languages:  eng     Pagination:  477-86     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Adrenergic beta-Antagonists / pharmacology*
Animals
Cytokines / biosynthesis*
Epinephrine / pharmacology*
Interleukin-1beta / biosynthesis
Interleukin-6 / biosynthesis
Male
Muscle, Skeletal / metabolism*
Protein Biosynthesis / drug effects*
RNA, Messenger / biosynthesis
Rats
Rats, Sprague-Dawley
Sepsis / metabolism*
Tumor Necrosis Factor-alpha / biosynthesis
Grant Support
ID/Acronym/Agency:
GM38032/GM/NIGMS NIH HHS; R01 GM038032/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Adrenergic beta-Antagonists; 0/Cytokines; 0/Interleukin-1beta; 0/Interleukin-6; 0/RNA, Messenger; 0/Tumor Necrosis Factor-alpha; YKH834O4BH/Epinephrine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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