title: Skeletal muscle growth in young rats is inhibited by chronic exposure to IL-6 but preserved by concurrent voluntary endurance exercise.
abstract: Childhood diseases are often accompanied by chronic inflammation, which is thought to negatively impact growth. Interleukin-6 (IL-6) is typically cited as an indicator of inflammation and is linked to impaired growth. This study was designed to isolate and identify potential effects of chronic IL-6 exposure on skeletal muscle growth during development. A second aim was to determine if endurance exercise, thought to antagonize chronic inflammation, would interact with any effects of IL-6. The muscles of one leg of rapidly growing rats were exposed to IL-6 or vehicle for 14 days. Subgroups of IL-6-infused rats were provided access to running wheels. Local IL-6 infusion resulted in approximately 13% muscle growth deficit (myofibrillar protein levels). Exercise (>4,000 m/day) prevented this deficit. IL-6 infusion increased mRNA for suppressor of cytokine signaling-3 (SOCS3) and tumor necrosis factor-alpha (TNF-alpha), and this was not prevented by exercise. IL-6 infusion increased the mRNAs for atrogin, insulin-like growth factor-I (IGF-I), and IGF binding protein-4 (IGFBP4), and these effects were mitigated by exercise. Exercise stimulated an increase in total RNA ( approximately 19%) only in the IL-6-infused muscle, suggesting that a compensatory increase in translational capacity was required to maintain muscle growth. This study indicates that IL-6 exposure during periods of rapid growth in young animals can retard growth possibly via interactions with key growth factors. Relatively high volumes of endurance-type exercise do not exacerbate the negative effects of IL-6 and in fact were found to be beneficial in protecting muscle growth.
authors.affiliation: Department of Physiology and Biophysics, University of California, Irvine, CA 92697-4560, USA.
authors.forename: P W
authors.initials: PW
authors.lastname: Bodell
authors.forename: E
authors.initials: E
authors.lastname: Kodesh
authors.forename: F
authors.initials: F
authors.lastname: Haddad
authors.forename: F P
authors.initials: FP
authors.lastname: Zaldivar
authors.forename: D M
authors.initials: DM
authors.lastname: Cooper
authors.forename: G R
authors.initials: GR
authors.lastname: Adams
mesh_terms: D000367:Age Factors; D000818:Animals; D005121:Extremities; D005260:Female; D018836:Inflammation Mediators / Q000008:administration & dosage / Q000378:metabolism*; D015918:Infusion Pumps, Implantable; D018974:Insulin-Like Growth Factor Binding Protein 4 / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D015850:Interleukin-6 / Q000008:administration & dosage / Q000378:metabolism*; D024510:Muscle Development; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000254:growth & development* / Q000378:metabolism; D010807:Physical Endurance; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins; D044843:SKP Cullin F-Box Protein Ligases / Q000378:metabolism; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D018836:Inflammation Mediators; D018974:Insulin-Like Growth Factor Binding Protein 4; D015850:Interleukin-6; D009124:Muscle Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; C491410:Socs3 protein, rat; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D014409:Tumor Necrosis Factor-alpha; D007334:Insulin-Like Growth Factor I; C486692:Fbxo32 protein, rat; D044843:SKP Cullin F-Box Protein Ligases