Submitted on July 24, 2008
Revised on September 10, 2008
Accepted on October 12, 2008
Contribution of IL-6 to the Hsp72, Hsp25, and 
-crystallin responses to inflammation and exercise training in mouse skeletal and cardiac muscle
Kimberly A. Huey1* and Benjamin M. Meador1
1 University of Illinois
* To whom correspondence should be addressed. E-mail: khuey{at}uiuc.edu.
The heat shock proteins (Hsp), Hsp72, Hsp25 and 
-crystallin (C) may protect tissues during exercise and/or inflammatory insults; however no studies have investigated whether exercise training increases both basal and inflammation-induced expression of these Hsps in skeletal or cardiac muscle. IL-6 is produced by muscle during both exercise and inflammation and has been shown to modulate Hsp expression. These studies tested the hypothesis that voluntary wheel running (RW) increases basal and inflammation-induced Hsp72, Hsp25 and C protein through an IL-6 dependent mechanism. We compared Hsp72, Hsp25, C, and IL-6 protein levels 4 h after systemic inflammation induced by lipopolysaccharide (LPS) in skeletal and cardiac muscles of wildtype (IL-6+/+) and IL-6 deficient (IL-6-/-) mice after 2 weeks of wheel running (RW) or normal cage activity (Sed). LPS significantly increased skeletal Hsp72 and Hsp25 relative to saline in Sed IL-6+/+, but not IL-6-/- mice. LPS increased Hsp72 relative to saline in Sed IL-6+/+ cardiac muscle. RW increased basal Hsp72, Hsp25 and C in skeletal muscle in IL-6+/+ and IL-6-/- mice. However, LPS was not associated with increases in any Hsp in RW IL-6+/+ or IL-6-/- mice. LPS increased IL-6 protein in skeletal muscle and plasma in Sed and RW groups, with a significantly greater response in RW. The major results provide the first in vivo evidence that the absence of IL-6 is associated with reduced skeletal muscle Hsp72 and Hsp25 responses to LPS, but that IL-6 is not required for exercise-induced Hsp up-regulation in skeletal or cardiac muscle.
