Crosstalk Between Skeletal Muscle and Immune System: Which Roles Do IL-6 and Glutamine Play?

Abstract

The skeletal muscle was always seen from biomechanical and biochemical views. It is well-established that an active muscle brings many benefits for different body organs and tissues, including the immune system. Since the 1970s, many studies have shown the importance of regular exercise and physical activity in increasing the body's ability to fight opportunist infections, as well as a strategy to fight established diseases. This interaction was mainly attributed to the glutamine, a non-essential amino acid produced by the active skeletal muscle and primarily consumed by rapidly dividing cells, including lymphocytes and monocytes/macrophages, as their main source of energy. Therefore, these cells' function would be significantly improved by the presence of a bigger glutamine pool, facilitating phagocytosis, antigen-presentation, proliferative capacity, cytokine synthesis and release, among other functions. Despite its importance, glutamine is not the only molecule to connect these two tissues. The presence of cytokines is crucial for a proper immune system function. Many of them have well-established pro-inflammatory properties, while others are known for their anti-inflammatory role. Interleukin-6 (IL-6), however, has been in the center of many scientific discussions since it can act as pro-and anti-inflammatory cytokine depending on the tissue that releases it. Skeletal muscle is an essential source of IL-6 with anti-inflammatory properties, regulating the function of the immune cells after tissue injury and the healing process. Therefore, this review aims to discuss further the role of these four components (glutamine, and interleukin-6, and its interface with monocytes/macrophages, and lymphocytes) on the communication between the skeletal muscle and the immune system.

Association and Interaction Between Serum Interleukin-6 Levels and Metabolic Dysfunction-Associated Fatty Liver Disease in Patients With Severe Coronavirus Disease 2019

“…Moreover, similar to liver, it is commonly to see COVID-19 affects the skeletal muscle such as loss of muscle mass, strength, and physical function ( 33 ). Skeletal muscle is also an essential source of IL-6 ( 34 ). Therefore, the COVID-19-muscle-IL-6 triangle is also worth investigating.…”

The Immune System in Duchenne Muscular Dystrophy Pathogenesis

“…The canine DMD model, the golden retriever muscular dystrophy (GRMD), suffers from a more severe phenotype than mdx mice, as pathological features are evident between 3 and 6 months of age, resembling those of DMD patients at 5-10 years [81]. In the last years, different works described biomarkers associated with the progression of the GRMD, as the over-expression of chitinase 3-like 1 (CHI3L1) [82] or the presence of CD49d+ circulating lymphocytes [83], useful to improve the clinical relevance of GRMD studies. In a preclinical context, we have intra-arterially transplanted autologous genetically corrected muscle derived CD133+ cells into GRMD dogs, which partially rescued the expression of dystrophin.…”

Wharton’s Jelly-Derived Mesenchymal Stem Cells Reduce Fibrosis in a Mouse Model of Duchenne Muscular Dystrophy by Upregulating microRNA 499

“…Members of the TGFβ family elicit cellular responses via TGFβRs, to activate the canonical SMAD pathway [ 43 , 44 ]. Improved muscle repair can be achieved not only by reducing fibrosis development but also by modifying the inflammatory response [ 45 , 46 ]. Upregulation of TGFβ activity accompanies inflammation and fibrosis and abolishes the homeostasis required for proper and efficient muscle regeneration [ 42 , 47 ].…”