The cytokine interleukin‐6 (IL‐6) is involved in a diverse set of physiological processes. Traditionally, IL‐6 has been thought of in terms of its inflammatory actions during the acute phase response and in chronic conditions such as rheumatoid arthritis and obesity. However, IL‐6 is also an important signaling molecule during exercise, being acutely released from working muscle fibers with increased exercise duration, intensity, and muscle glycogen depletion. In this context, IL‐6 enables muscle‐organ crosstalk, facilitating a coordinated response to help maintain muscle energy homeostasis, while also having anti‐inflammatory actions. The range of actions of IL‐6 can be explained by its dichotomous signaling pathways. Classical signaling involves IL‐6 binding to a cell‐surface receptor (mbIL‐6R; present on only a small number of cell types) and is the predominant signaling mechanism during exercise. Trans‐signaling involves IL‐6 binding to a soluble version of its receptor (sIL‐6R), with the resulting complex having a much greater half‐life and the ability to signal in all cell types. Trans‐signaling drives the inflammatory actions of IL‐6 and is the predominant pathway in disease. A single nucleotide polymorphism (rs2228145) on the IL‐6R gene can modify the classical/trans‐signaling balance through increasing the levels of sIL‐6R. This SNP has clinical significance, having been linked to inflammatory conditions such as rheumatoid arthritis and type 1 diabetes, as well as to the severity of symptoms experienced with COVID‐19. This review will describe how acute exercise, chronic training and the rs2228145 SNP can modify the IL‐6 signaling pathway and the consequent implications for health and athletic performance.

Acute increases in interleukin (IL)-6 following prolonged exercise are associated with the induction of a transient anti-inflammatory state (e.g., increases in IL-10) that is partly responsible for the health benefits of regular exercise. The purposes of this study were to investigate the IL-6–related inflammatory response to high-intensity interval exercise (HIIE) and to determine the impact of exercise intensity and volume on this response. Ten participants (5 males and 5 females) completed 3 exercise bouts of contrasting intensity and volume (LOW, MOD, and HIGH). The HIGH protocol was based upon standard HIIE protocols, while the MOD and LOW protocols were designed to enable a comparison of exercise intensity and volume with a fixed duration. Inflammatory cytokine concentrations were measured in plasma (IL-6, IL-10) and also determined the level of gene expression (IL-6, IL-10, and IL-4R) in peripheral blood. The plasma IL-6 response to exercise (reported as fold changes) was significantly greater in HIGH (2.70 ± 1.51) than LOW (1.40 ± 0.32) (P = 0.04) and was also positively correlated to the mean exercise oxygen uptake (r = 0.54, P < 0.01). However, there was no change in anti-inflammatory IL-10 or IL-4R responses in plasma or at the level of gene expression. HIIE caused a significant increase in IL-6 and was greater than that seen in low-intensity exercise of the same duration. The increases in IL-6 were relatively small in magnitude, and appear to have been insufficient to induce the acute systemic anti-inflammatory effects, which are evident following longer duration exercise.

IL-6 plays a mechanistic role in conditions such as metabolic syndrome, chronic fatigue syndrome and clinical depression and also plays a major role in inflammatory and immune responses to exercise. The purpose of this study was to investigate the levels of resting and post exercise IL-6 when measured in venous plasma, saliva and capillary plasma. Five male and five females completed 2 separate exercise trials, both of which involved standardized exercise sessions on a cycle ergometer. Venous blood and saliva samples were taken immediately before and after Trial A, venous and capillary blood samples were taken immediately before and after Trial B. IL-6 values were obtained using a high-sensitivity enzyme-linked immunosorbent assay (ELISA). In Trial A venous plasma IL-6 increased significantly from 0.4±0.14pg/ml to 0.99±0.29pg/ml (P<0.01) while there was no increase in salivary IL-6. Venous plasma and salivary IL-6 responses were not correlated at rest, post exercise or when expressed as an exercise induced change. In Trial B venous and capillary plasma IL-6 increased significantly (venous: 0.22±0.18 to 0.74±0.28pg/ml (P⩽0.01); capillary: 0.37±0.22 to 1.08±0.30pg/ml (P<0.01). Venous and capillary plasma responses did not correlate at rest (r=0.59, P=0.07) but did correlate post exercise (r=0.79, P⩾0.001) and when expressed as an exercise induced change (r=0.71, P=0.02). Saliva does not appear to reflect systemic IL-6 responses, either at rest or in response to exercise. Conversely, capillary plasma responses are reflective of systemic IL-6 responses to exercise.

This study investigated the effects of complete and partial sleep deprivation on multiple aspects of athletic performance. Ten males completed a cognitive function test, maximal handgrip strength, countermovement jump (CMJ) and a 15 min all out cycling test to assess aerobic performance. These tests were performed following 3 different sleep conditions; normal sleep (CON), a 4 hr sleep opportunity (PART) and complete sleep deprivation (DEP). Data were analysed using a Bayesian multi-level regression model to provide probabilities of impairment (p = %). Aerobic performance, CMJ and handgrip strength were impaired by 11.4% (p = 100%), 10.9% (p = 100%) and 6% (p = 97%) following DEP, while aerobic performance and CMJ were highly likely impaired by 4.1% (p = 90%) and 5.2% (p = 94%) following PART. Cognitive reaction time was not impacted by PART or DEP. In contrast the accuracy of responses was highly likely impaired by 2% (91) following DEP, while there was less certainty of impaired accuracy following PART (−1%, p = 73). Multiple aspects of physical and cognitive performance were impacted by sleep deprivation. The greatest detrimental effects were seen for aerobic performance and CMJ. Partial sleep deprivation equating to 4 hrs of sleep causes subtle, but potentially important negative impairments on athletic performance.

Exercise can induce numerous health benefits that can reduce the risk of chronic diseases and all-cause mortality, yet a significant percentage of the population do not meet minimal physical activity guidelines. Several recent studies have shown that passive heating can induce numerous health benefits, many of which are comparable with exercise, such as improvements to cardiorespiratory fitness, vascular health, glycemic control, and chronic low-grade inflammation. As such, passive heating is emerging as a promising therapy for populations who cannot perform sustained exercise or display poor exercise adherence. There appears to be some overlap between the cellular signaling responses that are regulated by temperature and the mechanisms that underpin beneficial adaptations to exercise, but detailed comparisons have not yet been made. Therefore, the purpose of this mini review is to assess the similarities and distinctions between adaptations to passive heating and exercise. Understanding the potential shared mechanisms of action between passive heating and exercise may help to direct future studies to implement passive heating more effectively and identify differences between passive heating and exercise-induced adaptations.

Introduction: An increased perception of effort and subjective fatigue are thought to be central to decreased exercise performance observed after disrupted sleep. However, there is limited understanding of mechanisms that underpin these phenomena. We investigated the role of interleukin-6 (IL-6), the soluble IL-6 receptor, and neuroendocrine factors (cortisol, adrenaline, noradrenaline, and brain-derived neurotropic factor) in mediating these responses at rest and during exercise.Methods: In a randomized order, 10 healthy active men completed three experimental trials following different sleep conditions: a single night of sleep deprivation, partial sleep deprivation equivalent to 4 h of sleep, and normal sleep. The experimental sessions consisted of physiological and perceptual measurements of exercise intensity throughout 45-min moderate intensity and 15-min maximal effort cycling. Cytokine and neuroendocrine factors were assessed at rest and in response to exercise.Results: Sleep deprivation resulted in increased resting IL-6, lower blood glucose, increased perceived fatigue and perception of effort, lower free-living energy expenditure, and reduced maximal exercise performance. In contrast, sleep deprivation did not alter physiological, cytokine, or neuroendocrine responses to exercise. Variations in the resting concentration of IL-6 were associated with lowered blood glucose, an increased perception of effort, and impaired exercise performance. Resting concentrations of cortisol, adrenaline, noradrenaline, and BNDF showed subtle interactions with specific aspects of mood status and performance but were not affected by sleep deprivation. There were minimal effects of partial sleep deprivation.Conclusions: These findings demonstrate that cytokine and neuroendocrine responses to exercise are not altered by sleep deprivation but that changes in the resting concentration of IL-6 may play a role in altered perception of effort in this context.