Neutrophil and monocyte responses to downhill running: Intracellular contents of MPO, IL‐6, IL‐10, pstat3, and SOCS3

High‐intensity exercise results in immune activation. This study determined whether (a) there is concordance between serum MPO and neutrophil and/or monocyte intracellular MPO content; (b) peripheral blood mononuclear cells respond to inflammatory interleukins (ILs) by increasing intracellular signaling. Healthy male (n = 12) volunteers participated in high‐intensity running (12 × 5 min, 10% decline, 15 km/h). Blood sample (pre, post, 4 h) analyses included serum concentrations of IL‐1β, IL‐1ra, IL‐4, IL‐6, IL‐8, IL‐10, matrix metalloprotease‐9 (MMP‐9) and creatine kinase (CK). Intracellular IL‐6, IL‐10, MPO and STAT3/SOCS3 signaling were assessed in mononuclear cells. CK (1573 ± 756 u/L), MMP‐9 (101 ± 27 ng/mL), neutrophil (9.89 ± 0.76 × 109 cells/L) and monocyte counts (1 ± 0.08 × 109 cells/L) increased at 4 h. At 4 h serum (7.1 ± 1.3 ng/mL) and monocyte MPO (1.7‐fold) increased, whereas neutrophil MPO decreased (0.8‐fold). Intracellular monocyte IL‐10 and IL‐6 decreased by 15% and 20–30%, respectively, coinciding with elevations in serum IL‐10 of 14.5 ± 4.7 pg/mL and IL‐6 of 5.4 ± 2.9 pg/mL, suggesting immune cell cytokine release in response to exercise. Intracellular PBMC p‐STAT3 to total STAT3 ratio increased from pre to 4 h. Circulating monocytes are responsive to increased serum IL‐6 suggesting a negative feedback loop via STAT3 signaling.

[1]  Y. Ohira,et al.  Anti-interleukin-6 receptor antibody (MR16-1) promotes muscle regeneration via modulation of gene expressions in infiltrated macrophages. , 2014, Biochimica et biophysica acta.

[2]  K. Myburgh,et al.  Variable inflammation and intramuscular STAT3 phosphorylation and myeloperoxidase levels after downhill running , 2014, Scandinavian journal of medicine & science in sports.

[3]  Diana Boraschi,et al.  MafB is a downstream target of the IL-10/STAT3 signaling pathway, involved in the regulation of macrophage de-activation. , 2014, Biochimica et biophysica acta.

[4]  John W. Chen,et al.  Molecular Imaging of Macrophage Enzyme Activity in Cardiac Inflammation , 2014, Current Cardiovascular Imaging Reports.

[5]  K. Myburgh,et al.  Contusion injury with chronic in vivo polyphenol supplementation: leukocyte responses. , 2014, Medicine and science in sports and exercise.

[6]  Y. Kawakami,et al.  Eccentric exercise-induced delayed-onset muscle soreness and changes in markers of muscle damage and inflammation. , 2013, Exercise immunology review.

[7]  B. Chazaud,et al.  Monocyte/macrophage interactions with myogenic precursor cells during skeletal muscle regeneration , 2013, The FEBS journal.

[8]  A. Bulmer,et al.  Transcriptome analysis of neutrophils after endurance exercise reveals novel signaling mechanisms in the immune response to physiological stress. , 2013, Journal of applied physiology.

[9]  Xiaonan H. Wang,et al.  Interleukin-6/Signal Transducer and Activator of Transcription 3 (STAT3) Pathway Is Essential for Macrophage Infiltration and Myoblast Proliferation during Muscle Regeneration* , 2012, The Journal of Biological Chemistry.

[10]  A. Jurka,et al.  The Relationship Between Maximal Exercise‐Induced Increases in Serum IL‐6, MPO and MMP‐9 Concentrations , 2012, Scandinavian journal of immunology.

[11]  S. Tighe,et al.  Changes in transcriptional output of human peripheral blood mononuclear cells following resistance exercise , 2011, European Journal of Applied Physiology.

[12]  M. Tarnopolsky,et al.  IL-6 Induced STAT3 Signalling Is Associated with the Proliferation of Human Muscle Satellite Cells Following Acute Muscle Damage , 2011, PloS one.

[13]  J. Tidball,et al.  Interleukin-10 reduces the pathology of mdx muscular dystrophy by deactivating M1 macrophages and modulating macrophage phenotype. , 2011, Human molecular genetics.

[14]  O. Hue,et al.  Effect of strenuous physical exercise on circulating cell-derived microparticles. , 2011, Clinical hemorheology and microcirculation.

[15]  J. Arnhold,et al.  Human myeloperoxidase in innate and acquired immunity. , 2010, Archives of biochemistry and biophysics.

[16]  R. Nagai,et al.  Pentraxin3 and high-sensitive C-reactive protein are independent inflammatory markers released during high-intensity exercise , 2010, European Journal of Applied Physiology.

[17]  T. Putoczki,et al.  ReviewStat 3 : linking inflammation to epithelial cancer-more than a " gut " feeling ? , 2015 .

[18]  J. Tidball,et al.  Regulatory interactions between muscle and the immune system during muscle regeneration. , 2010, American journal of physiology. Regulatory, integrative and comparative physiology.

[19]  J. Hallén,et al.  Time course of leukocyte accumulation in human muscle after eccentric exercise. , 2010, Medicine and science in sports and exercise.

[20]  Shlomit Radom-Aizik,et al.  A brief bout of exercise alters gene expression and distinct gene pathways in peripheral blood mononuclear cells of early- and late-pubertal females. , 2009, Journal of applied physiology.

[21]  D. Cooper,et al.  Effects of 30 min of aerobic exercise on gene expression in human neutrophils. , 2008, Journal of applied physiology.

[22]  S. Semple,et al.  Changes in serum cytokines after repeated bouts of downhill running. , 2007, Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme.

[23]  T. Raastad,et al.  Delayed leukocytosis and cytokine response to high-force eccentric exercise. , 2005, Medicine and science in sports and exercise.

[24]  Kazunori Nosaka,et al.  Exercise-induced muscle damage, plasma cytokines, and markers of neutrophil activation. , 2005, Medicine and science in sports and exercise.

[25]  G. W. Hatfield,et al.  Effects of exercise on gene expression in human peripheral blood mononuclear cells. , 2004, Journal of applied physiology.

[26]  Katsuhiko Suzuki,et al.  Changes in neutrophil surface receptor expression, degranulation, and respiratory burst activity after moderate- and high-intensity exercise. , 2004, Journal of applied physiology.

[27]  J. Tidball,et al.  Null Mutation of gp91phox Reduces Muscle Membrane Lysis During Muscle Inflammation in Mice , 2003, The Journal of physiology.

[28]  Rolf Rossaint,et al.  Activation of STAT3 by IL-6 and IL-10 in Primary Human Macrophages Is Differentially Modulated by Suppressor of Cytokine Signaling 3 1 , 2003, The Journal of Immunology.

[29]  V. Morozov,et al.  Effect of exercise to exhaustion on myeloperoxidase and lysozyme release from blood neutrophils , 2003, European Journal of Applied Physiology.

[30]  A. Yoshimura,et al.  Involvement of Suppressor of Cytokine Signaling-3 as a Mediator of the Inhibitory Effects of IL-10 on Lipopolysaccharide-Induced Macrophage Activation1 , 2002, The Journal of Immunology.

[31]  H. Ziegler-Heitbrock,et al.  Role of Stat3 in Lipopolysaccharide-Induced IL-10 Gene Expression1 , 2000, The Journal of Immunology.

[32]  D. Holbert,et al.  Differential white cell count after two bouts of downhill running. , 1998, International journal of sports medicine.

[33]  The JAK-STAT Signaling Pathway: Input and Output Integration , 2022 .