Skeletal myocytes are a source of interleukin‐6 mRNA expression and protein release during contraction: evidence of fiber type specificity

Abstract

In this study, we aimed to determine whether skeletal muscle cells per se are a source of interleukin (IL)-6 during contraction and whether IL-6 production is fiber type specific. Muscle biopsy samples were collected from seven males before (PRE) and after (POST) completing 120 min of continuous bicycle ergometry. Biopsies were sectioned and analyzed for the following: IL-6 protein detected by immunohistochemistry (IHC), IL-6 mRNA content detected by in situ hybridization, fiber type measured by either IHC or myofibrillar ATPase activity stain, and glycogen content measured by periodic acid schiff (PAS) assay. Fibers were qualitatively categorized according to glycogen content to one of five groups (1-5), with 1 being very low (LOW) and 5 being very high (HIGH) glycogen. Total fluorescence (PRE vs. POST) and glycogen-dependent fluorescence (LOW vs. HIGH) of IL-6 protein were quantitated using Metamorph software. Total IL-6 protein was elevated from PRE to POST exercise (P<0.05). At PRE, IL-6 protein was evenly distributed across all fibers at low levels, consistent with glycogen distribution. At POST, IL-6 protein was greater (P<0.05) in HIGH compared with LOW glycogen fibers, which coincided with type 2 fibers. IL-6 mRNA was distributed peripherally in all fibers at PRE. At POST, however, IL-6 mRNA appeared predominantly in type 2 fibers, which also had higher glycogen content (P<0.05). These data demonstrate that myocytes per se are a source of IL-6 produced during contraction. Our data also suggest that type 2 fibers predominantly produce IL-6 during muscle contractile activity.

IL-6 deficiency in mice neither impairs induction of metabolic genes in the liver nor affects blood glucose levels during fasting and moderately intense exercise

“…IL-6 was found to be a myokine that is produced within the contracting muscle fibres [21] and released into the circulation depending on intensity and duration of exercise [22,23]. Further research revealed that IL-6 fulfils some criteria of an exercise factor, because it stimulates glucose uptake [24,25] and fatty acid oxidation in skeletal muscle [26,27], increases lipolysis [28] and activates AMP-activated protein kinase [29].…”

Myokines in insulin resistance and type 2 diabetes

“…Upon muscle contraction, IL-6 is released into the circulation the amount of which is dependent on intensity and duration of exercise [10] and the energy status of a muscle, as determined by pre-exercise glycogen content [11]. This leads to an acute increase of IL-6 plasma levels during exercise, the main sources of which are the myofibres [12].…”

Plasma IL-6 levels during arm exercise in persons with spinal cord injury

“…These results indicate that arm crank exercise induces changes in plasma IL-6 kinetics that are different from those of lower-body cycling exercise. Hiscock et al 20 reported that the source of IL-6 was the myocytes in exercising leg muscles at 55%VO 2 max. Therefore, we assumed the increase of IL-6 during arm exercise might come from contracting arm muscles; however, the mechanism of IL-6 production during arm crank exercise is not clear at present.…”