Abstract
A transient increase in local pro-inflammatory cytokine expression following skeletal muscle injury mediates the repair and regeneration of damaged myofibers through myogenesis. Regenerative capacity is diminished and muscle wasting occurs, however, when intramuscular inflammatory signaling is exceedingly high or persists chronically. An excessive and persistent inflammatory response to muscle injury may therefore impair recovery by limiting the repair of damaged tissue and triggering muscle atrophy. The concentration-dependent activation of different downstream signaling pathways by several pro-inflammatory cytokines in cell and animal models support these opposing roles of post-injury inflammation. Understanding these molecular pathways is essential in developing therapeutic strategies to attenuate excessive inflammation and accelerate functional recovery and muscle mass accretion following muscle damage. This is especially relevant given the observation that basal levels of intramuscular inflammation and the inflammatory response to muscle damage are not uniform across all populations, suggesting certain individuals may be more susceptible to an excessive inflammatory response to injury that limits recovery. This narrative review explores the opposing roles of intramuscular inflammation in muscle regeneration and muscle protein turnover. Factors contributing to an exceedingly high inflammatory response to damage and age-related impairments in regenerative capacity are also considered.
Highlights
Skeletal muscle is the most abundant tissue in the human body, with a vital role in energy and protein metabolism as well as force generation for locomotion and stability
Macrophages are initially polarized into a pro-inflammatory M1 phenotype that secretes pro-inflammatory cytokines (i.e., tumor necrosis factor-α (TNFα), IL-1β, IFN-γ) and reactive oxygen species to facilitate the removal of cellular debris and recruitment of immune cells to the lesion site (Villalta et al, 2009; Dort et al, 2019)
The involvement of multiple cytokines under physiological conditions and the varied concentrations of cytokines between plasma and muscle interstitium due to the presence of an endothelial barrier are possible confounding factors that must be considered. Regardless, these findings collectively suggest that a transient increase in intramuscular pro-inflammatory signaling after injury is required for muscle regeneration and repair, while an excessive or persistent inflammatory response can prevent myogenesis and limit recovery
Summary
The concentration-dependent activation of different downstream signaling pathways by several pro-inflammatory cytokines in cell and animal models support these opposing roles of post-injury inflammation Understanding these molecular pathways is essential in developing therapeutic strategies to attenuate excessive inflammation and accelerate functional recovery and muscle mass accretion following muscle damage. This is especially relevant given the observation that basal levels of intramuscular inflammation and the inflammatory response to muscle damage are not uniform across all populations, suggesting certain individuals may be more susceptible to an excessive inflammatory response to injury that limits recovery This narrative review explores the opposing roles of intramuscular inflammation in muscle regeneration and muscle protein turnover.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
