Cross-talk between skeletal muscle and immune cells: muscle-derived mediators and metabolic implications

Am J Physiol Endocrinol Metab. 2013 Mar 1;304(5):E453-65. doi: 10.1152/ajpendo.00553.2012. Epub 2012 Dec 31.


Skeletal muscles contain resident immune cell populations and their abundance and type is altered in inflammatory myopathies, endotoxemia or different types of muscle injury/insult. Within tissues, monocytes differentiate into macrophages and polarize to acquire pro- or anti-inflammatory phenotypes. Skeletal muscle macrophages play a fundamental role in repair and pathogen clearance. These events require a precisely regulated cross-talk between myofibers and immune cells, involving paracrine/autocrine and contact interactions. Skeletal muscle also undergoes continuous repair as a result of contractile activity that involves participation of myokines and anti-inflammatory input. Finally, skeletal muscle is the major site of dietary glucose disposal; therefore, muscle insulin resistance is essential to the development of whole body insulin resistance. Notably, muscle inflammation is emerging as a potential contributor to insulin resistance. Recent reports show that inflammatory macrophage numbers within muscle are elevated during obesity and that muscle cells in vitro can mount autonomous inflammatory responses under metabolic challenge. Here, we review the nature of skeletal muscle inflammation associated with muscle exercise, damage, and regeneration, endotoxin presence, and myopathies, as well as the new evidence of local inflammation arising with obesity that potentially contributes to insulin resistance.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Diabetes Mellitus / physiopathology
  • Dietary Fats / pharmacology
  • Humans
  • Immune System / physiology*
  • Inflammation Mediators / metabolism
  • Inflammation Mediators / physiology
  • Macrophages / immunology
  • Muscle, Skeletal / metabolism*
  • Muscle, Skeletal / physiology*
  • Muscular Diseases / metabolism
  • Muscular Diseases / physiopathology
  • Obesity / physiopathology
  • Receptor Cross-Talk / physiology*


  • Dietary Fats
  • Inflammation Mediators