IL-6 signaling blockade increases inflammation but does not affect muscle function in the mdx mouse.
BACKGROUND
IL-6 is a pleiotropic cytokine that modulates inflammatory responses and plays critical roles in muscle maintenance and remodeling. In the mouse model (mdx) of Duchenne Muscular Dystrophy, IL-6 and muscle inflammation are elevated, which is believed to contribute to the chronic inflammation and failure of muscle regeneration in DMD. The purpose of the current study was to examine the effect of blocking IL-6 signaling on the muscle phenotype including muscle weakness and pathology in the mdx mouse.


METHODS
A monoclonal antibody against the IL-6 receptor (IL-6r mAb) that blocks local and systemic IL-6 signaling was administered to mdx and BL-10 mice for 5 weeks and muscle function, histology, and inflammation were examined.


RESULTS
IL-6r mAb treatment increased mdx muscle inflammation including total inflammation score and ICAM-1 positive lumens in muscles. There was no significant improvement in muscle strength nor muscle pathology due to IL-6r mAb treatment in mdx mice.


CONCLUSIONS
These results showed that instead of reducing inflammation, IL-6 signaling blockade for 5 weeks caused an increase in muscle inflammation, with no significant change in indices related to muscle regeneration and muscle function. The results suggest a potential anti-inflammatory instead of the original hypothesized pro-inflammatory role of IL-6 signaling in the mdx mice.
Laboratory of Muscle and Translational Therapeutics, Department of Exercise Science, University of South Carolina, Columbia, SC, USA. mkostek@mailbox.sc.edu
Matthew C
MC
Kostek
Kanneboyina
K
Nagaraju
Emidio
E
Pistilli
Arpana
A
Sali
San-Huei
SH
Lai
Brad
B
Gordon
Yi-Wen
YW
Chen
D000818:Animals; D000911:Antibodies, Monoclonal / Q000633:toxicity; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors* / Q000502:physiology*; D015850:Interleukin-6 / Q000378:metabolism / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D053580:Muscle Strength / Q000187:drug effects / Q000502:physiology; D018482:Muscle, Skeletal / Q000502:physiology*; D020388:Muscular Dystrophy, Duchenne / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology*; D011897:Random Allocation; D019947:Receptors, Interleukin-6 / Q000276:immunology; D015398:Signal Transduction / Q000502:physiology*; D000093242:Interleukin-6 Inhibitors
D000911:Antibodies, Monoclonal; D018836:Inflammation Mediators; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D000093242:Interleukin-6 Inhibitors; C577686:interleukin-6, mouse