Cytokines in skeletal muscle growth and decay

Abstract

By definition, cytokines are the first messengers of intercellular communications observed among leukocytes. Numerous cytokines control immune system and biological reactions thereof, but are functionally grouped into proand anti-inflammatory varieties (the latter are also involved in allergic reactions). The bulk of evidence points to substantial role played by cytokines in skeletal muscle growth and wasting. Cytokines and growth factors of immune origin affect skeletal muscle growth and organ formation, regeneration, and wasting but are also produced and secreted by muscle fibers as myokines. To orchestrate skeletal muscle growth, hepatocyte growth factor/scatter factor (HGF/SF) and insulinlike growth factors (IGF-I and IGF-II) play the primary physiological role being mediated through PI3-K/Akt signaling pathway. Skeletal muscle mass is in turn controlled negatively by myostatin, a member of transforming growth factor beta (TGF-β) superfamily. Following muscle injury, the immune-derived cytokines are most important in activation of muscle satellite cells: tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6); with IL-8 to arrange growth/regeneration; and IL-15 to control muscle hypertrophy. Some life-threatening diseases are associated with muscle wasting featured by accelerated muscle protein breakdown. In these catabolic states, cytokines such as TNF-α was often reported as causal factor. Moreover, cross talk between myokines (IL-6, IL-15) and adipokines (leptin) is vital for correct metabolic interorgan relations. Thus, cytokines and growth factors exist as basic chemical signals that orchestrate skeletal muscle fate in normal and diseased states.