Submitted on June 27, 2008
Revised on November 24, 2008
Accepted on December 2, 2008
Skeletal muscle growth in young rats is inhibited by chronic exposure to IL-6 but preserved by concurrent voluntary endurance exercise
Paul W. Bodell1, Einat Kodesh2, Fadia Haddad3, Frank P. Zaldivar1, Dan M. Cooper4, and Gregory R. Adams1*
1 University of California, Irvine
2 The Hebrew University
3 University of California at Irvine
4 University of California @ Irvine College of Medicine
* To whom correspondence should be addressed. E-mail: gradams{at}uci.edu.
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 ~13% muscle growth deficit (myofibrillar protein levels). Exercise (>4000m-day-1) prevented this deficit. IL-6 infusion increased mRNA for suppressor of cytokine signaling-3 (SOCS3) and tumor necrosis factor-
(TNF), 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 (~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.
