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      Acute Changes in Inflammatory Biomarker Levels in Recreational Runners Participating in a Marathon or Half-Marathon

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          Abstract

          Background

          Strenuous physical activity activates the participant’s immune responses; however, few studies exist, observing exercise-induced simultaneous changes in mediators of inflammation.

          Methods

          We examined individual responses in soluble urokinase-type plasminogen activator receptor (suPAR), a marker of immune activation, soluble endocytic receptor for haptoglobin-hemoglobin complexes (CD163), a marker of monocyte-macrophage activation, C-reactive protein (CRP), and pro- and anti-inflammatory cytokines from blood samples drawn at baseline, at 3- and 48-h post-races from recreational runners who successfully completed the marathon (199 ± 8 min, n = 4) or half-marathon (132 ± 4 min, n = 4) run. For comparisons, biomarkers reflecting muscle, heart, kidney, and liver functions were measured.

          Results

          Significant 3-h post-race increases occurred in levels of suPAR ( p < 0.01), CD163 ( p < 0.05), white blood cells ( p < 0.001), pro-inflammatory cytokines, interleukin-6 (IL-6) ( p < 0.001), IL-8 ( p < 0.05), and anti-inflammatory cytokine IL-10 ( p < 0.05), whereas tumor necrosis factor-α (TNF-α) and transforming growth factor-β (TGF-β) remained relatively stable. Full-marathon running lead to more pronounced increases in suPAR, CD163, IL-8, and IL-10 than half-marathon running. In addition, 3-h post-race increases of all these parameters correlated significantly with changes in serum TNF-α and cortisol. The 48-h levels of serum suPAR and both pro- and anti-inflammatory cytokines had decreased to baseline levels, whereas CRP, a marker of acute phase response, increased in those with the most prominent IL-6 and IL-10 elevations in their preceding samples. The highest suPAR, CRP, IL-6, TNF-α, IL-10, and cortisol levels were noted in the individual with the most severe post-race fatigue.

          Conclusions

          Prolonged running increases mediators of inflammation in an exercise-dose-dependent manner which should be considered in the assessment of health status of physically active individuals after recent acute bouts of strenuous exercise.

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          Most cited references29

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          Muscles, exercise and obesity: skeletal muscle as a secretory organ.

          During the past decade, skeletal muscle has been identified as a secretory organ. Accordingly, we have suggested that cytokines and other peptides that are produced, expressed and released by muscle fibres and exert either autocrine, paracrine or endocrine effects should be classified as myokines. The finding that the muscle secretome consists of several hundred secreted peptides provides a conceptual basis and a whole new paradigm for understanding how muscles communicate with other organs, such as adipose tissue, liver, pancreas, bones and brain. However, some myokines exert their effects within the muscle itself. Thus, myostatin, LIF, IL-6 and IL-7 are involved in muscle hypertrophy and myogenesis, whereas BDNF and IL-6 are involved in AMPK-mediated fat oxidation. IL-6 also appears to have systemic effects on the liver, adipose tissue and the immune system, and mediates crosstalk between intestinal L cells and pancreatic islets. Other myokines include the osteogenic factors IGF-1 and FGF-2; FSTL-1, which improves the endothelial function of the vascular system; and the PGC-1α-dependent myokine irisin, which drives brown-fat-like development. Studies in the past few years suggest the existence of yet unidentified factors, secreted from muscle cells, which may influence cancer cell growth and pancreas function. Many proteins produced by skeletal muscle are dependent upon contraction; therefore, physical inactivity probably leads to an altered myokine response, which could provide a potential mechanism for the association between sedentary behaviour and many chronic diseases.
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            Interleukin‐6 myokine signaling in skeletal muscle: a double‐edged sword?

            Interleukin (IL)‐6 is a cytokine with pleiotropic functions in different tissues and organs. Skeletal muscle produces and releases significant levels of IL‐6 after prolonged exercise and is therefore considered as a myokine. Muscle is also an important target of the cytokine. IL‐6 signaling has been associated with stimulation of hypertrophic muscle growth and myogenesis through regulation of the proliferative capacity of muscle stem cells. Additional beneficial effects of IL‐6 include regulation of energy metabolism, which is related to the capacity of actively contracting muscle to synthesize and release IL‐6. Paradoxically, deleterious actions for IL‐6 have also been proposed, such as promotion of atrophy and muscle wasting. We review the current evidence for these apparently contradictory effects, the mechanisms involved and discuss their possible biological implications.
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              Soluble CD163.

              J Möller (2012)
              CD163 is an endocytic receptor for haptoglobin-hemoglobin complexes and is expressed solely on macrophages and monocytes. As a result of ectodomain shedding, the extracellular portion of CD163 circulates in blood as a soluble protein (sCD163) at 0.7-3.9 mg/l in healthy individuals. The function of sCD163 is unknown, but during inflammation and macrophage activation, sCD163 levels increase acutely due to metalloproteinase-mediated cleavage near the cell membrane. It is now evident that sCD163 is very useful as a biomarker of macrophage activation in various inflammatory diseases, such as macrophage activation syndrome, sepsis, and liver disease. Moreover, sCD163 is a general risk marker of comorbidity and mortality in several chronic inflammatory disease states. Recently, sCD163 has been shown to be strongly associated with later development of type 2 diabetes in both lean and obese subjects, likely due to macrophage infiltration of adipose tissue and the liver. This review summarizes the current knowledge on the regulation of sCD163 in normal and pathological states and also deals with analytical aspects of sCD163 measurements in biological samples.
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                Author and article information

                Contributors
                +358 6 415 4719 , onni.niemela@epshp.fi
                Journal
                Sports Med Open
                Sports Med Open
                Sports Medicine - Open
                Springer International Publishing (Cham )
                2198-9761
                2 March 2016
                2 March 2016
                December 2016
                : 2
                : 1
                : 21
                Affiliations
                [1 ]Department of Surgery, Oulu University Hospital, P.O. Box 21, 90029 OYS Oulu, Finland
                [2 ]Department of Laboratory Medicine and Medical Research Unit, Seinäjoki Central Hospital and University of Tampere, Hanneksenrinne 7, 60220 Seinäjoki, Finland
                [3 ]Medical Informatics and Statistics Research Group, University of Oulu, Oulu, Finland
                Article
                45
                10.1186/s40798-016-0045-0
                5005625
                27747777
                b4cdeb9f-0c8b-4fdf-bba7-0b92fe67d45d
                © Niemelä et al. 2016

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 28 November 2015
                : 22 February 2016
                Categories
                Original Research Article
                Custom metadata
                © The Author(s) 2016

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