IMPORTANCE OF THE INNATE IMMUNE RESPONSE IN SKELETAL MUSCLE TO SEPSIS-INDUCED ALTERATIONS IN PROTEIN BALANCE.

There is growing appreciation that skeletal muscle is a fully functional component of the body's innate immune system with the potential to actively participate in the host response to invading bacteria as opposed to being a passive target. In this regard, skeletal muscle in general and myocytes specifically possess an afferent limb that recognizes a wide variety of host pathogens via their interaction with multiple classes of cell membrane-bound and intracellular receptors, including toll-like receptors, cytokine receptors, NOD-like receptors, and the NLRP inflammasome. The efferent limb of the innate immune system in muscle is equally robust and with an increased synthesis and secretion of a variety of myocyte-derived cytokines (i.e., myokines), including TNF-α, IL-1, IL-6, and NO as well as multiple chemokines in response to appropriate stimulation. Herein, the current narrative review focuses primarily on the immune response of myocytes per se as opposed to other cell types within whole muscle. Moreover, because there are important differences, this review focuses specifically on systemic infection and inflammation as opposed to the response of muscle to direct injury and various types of muscular dystrophies. To date, however, there are few definitive muscle-specific studies that are necessary to directly address the relative importance of muscle-derived immune activation as a contributor to either the systemic immune response or the local immune microenvironment within muscle during sepsis and the resultant downstream metabolic disturbances.