Acute Exercise and NK Cell Regulation in Tissue and Circulation After IL-6R Blockade

Summary

The study is a randomized controlled trial studying the acute effect of intense aerobic exercise upon NK (Natural Killer) cell activation and appetite-regulation in human participants with or without concommitant IL-6R receptor blockade (Tocilizumab)

Timeline

Start

2021-03-15

Primary completion

2021-10-04

Completion

2021-10-04

Publications

• Background Amar, D., Lindholm, M. E., Norrbom, J., Wheeler, M. T., Rivas, M., & Ashley, E. A. (2020). Differential Response Trajectories to Acute Exercise in Blood and Muscle. SSRN Electronic Journal, 1-43. https://doi.org/10.2139/ssrn.3508810
• Background Bergstrom J. Percutaneous needle biopsy of skeletal muscle in physiological and clinical research. Scand J Clin Lab Invest. 1975 Nov;35(7):609-16. No abstract available.
• Background Bigley AB, Rezvani K, Chew C, Sekine T, Pistillo M, Crucian B, Bollard CM, Simpson RJ. Acute exercise preferentially redeploys NK-cells with a highly-differentiated phenotype and augments cytotoxicity against lymphoma and multiple myeloma target cells. Brain Behav Immun. 2014 Jul;39:160-71. doi: 10.1016/j.bbi.2013.10.030. Epub 2013 Nov 5.
• Background Chan CJ, Smyth MJ, Martinet L. Molecular mechanisms of natural killer cell activation in response to cellular stress. Cell Death Differ. 2014 Jan;21(1):5-14. doi: 10.1038/cdd.2013.26. Epub 2013 Apr 12.
• Background Christensen JF, Simonsen C, Hojman P. Exercise Training in Cancer Control and Treatment. Compr Physiol. 2018 Dec 13;9(1):165-205. doi: 10.1002/cphy.c180016.
• Background Dogra P, Rancan C, Ma W, Toth M, Senda T, Carpenter DJ, Kubota M, Matsumoto R, Thapa P, Szabo PA, Li Poon MM, Li J, Arakawa-Hoyt J, Shen Y, Fong L, Lanier LL, Farber DL. Tissue Determinants of Human NK Cell Development, Function, and Residence. Cell. 2020 Feb 20;180(4):749-763.e13. doi: 10.1016/j.cell.2020.01.022. Epub 2020 Feb 13.
• Background Ghanemi A, St-Amand J. Interleukin-6 as a "metabolic hormone". Cytokine. 2018 Dec;112:132-136. doi: 10.1016/j.cyto.2018.06.034. Epub 2018 Jul 6.
• Background Gjevestad GO, Holven KB, Ulven SM. Effects of Exercise on Gene Expression of Inflammatory Markers in Human Peripheral Blood Cells: A Systematic Review. Curr Cardiovasc Risk Rep. 2015;9(7):34. doi: 10.1007/s12170-015-0463-4.
• Background Gupta P, Bigley AB, Markofski M, Laughlin M, LaVoy EC. Autologous serum collected 1 h post-exercise enhances natural killer cell cytotoxicity. Brain Behav Immun. 2018 Jul;71:81-92. doi: 10.1016/j.bbi.2018.04.007. Epub 2018 Apr 12.
• Background Hanna J, Bechtel P, Zhai Y, Youssef F, McLachlan K, Mandelboim O. Novel insights on human NK cells' immunological modalities revealed by gene expression profiling. J Immunol. 2004 Dec 1;173(11):6547-63. doi: 10.4049/jimmunol.173.11.6547.
• Background Kenfield SA, Stampfer MJ, Giovannucci E, Chan JM. Physical activity and survival after prostate cancer diagnosis in the health professionals follow-up study. J Clin Oncol. 2011 Feb 20;29(6):726-32. doi: 10.1200/JCO.2010.31.5226. Epub 2011 Jan 4.
• Background Larrabee RC. Leucocytosis after violent Exercise. J Med Res. 1902 Jan;7(1):76-82. No abstract available.
• Background Larsen SK, Gao Y, Basse PH. NK cells in the tumor microenvironment. Crit Rev Oncog. 2014;19(1-2):91-105. doi: 10.1615/critrevoncog.2014011142.
• Background Lukaski HC. Soft tissue composition and bone mineral status: evaluation by dual-energy X-ray absorptiometry. J Nutr. 1993 Feb;123(2 Suppl):438-43.
• Background Macpherson RE, Huber JS, Frendo-Cumbo S, Simpson JA, Wright DC. Adipose Tissue Insulin Action and IL-6 Signaling after Exercise in Obese Mice. Med Sci Sports Exerc. 2015 Oct;47(10):2034-42. doi: 10.1249/MSS.0000000000000660.
• Background Meyerhardt JA, Giovannucci EL, Ogino S, Kirkner GJ, Chan AT, Willett W, Fuchs CS. Physical activity and male colorectal cancer survival. Arch Intern Med. 2009 Dec 14;169(22):2102-8. doi: 10.1001/archinternmed.2009.412.
• Background Nieman DC, Miller AR, Henson DA, Warren BJ, Gusewitch G, Johnson RL, Davis JM, Butterworth DE, Nehlsen-Cannarella SL. Effects of high- vs moderate-intensity exercise on natural killer cell activity. Med Sci Sports Exerc. 1993 Oct;25(10):1126-34.
• Background Ostrowski K, Rohde T, Asp S, Schjerling P, Pedersen BK. Pro- and anti-inflammatory cytokine balance in strenuous exercise in humans. J Physiol. 1999 Feb 15;515 ( Pt 1)(Pt 1):287-91. doi: 10.1111/j.1469-7793.1999.287ad.x.
• Background Pedersen BK, Hoffman-Goetz L. Exercise and the immune system: regulation, integration, and adaptation. Physiol Rev. 2000 Jul;80(3):1055-81. doi: 10.1152/physrev.2000.80.3.1055.
• Background Pedersen L, Idorn M, Olofsson GH, Lauenborg B, Nookaew I, Hansen RH, Johannesen HH, Becker JC, Pedersen KS, Dethlefsen C, Nielsen J, Gehl J, Pedersen BK, Thor Straten P, Hojman P. Voluntary Running Suppresses Tumor Growth through Epinephrine- and IL-6-Dependent NK Cell Mobilization and Redistribution. Cell Metab. 2016 Mar 8;23(3):554-62. doi: 10.1016/j.cmet.2016.01.011. Epub 2016 Feb 16.
• Background Perez SA, Mahaira LG, Demirtzoglou FJ, Sotiropoulou PA, Ioannidis P, Iliopoulou EG, Gritzapis AD, Sotiriadou NN, Baxevanis CN, Papamichail M. A potential role for hydrocortisone in the positive regulation of IL-15-activated NK-cell proliferation and survival. Blood. 2005 Jul 1;106(1):158-66. doi: 10.1182/blood-2004-08-3232. Epub 2005 Mar 8.
• Background Radom-Aizik S, Zaldivar F, Haddad F, Cooper DM. Impact of brief exercise on peripheral blood NK cell gene and microRNA expression in young adults. J Appl Physiol (1985). 2013 Mar 1;114(5):628-36. doi: 10.1152/japplphysiol.01341.2012. Epub 2013 Jan 3.
• Background Rooney BV, Bigley AB, LaVoy EC, Laughlin M, Pedlar C, Simpson RJ. Lymphocytes and monocytes egress peripheral blood within minutes after cessation of steady state exercise: A detailed temporal analysis of leukocyte extravasation. Physiol Behav. 2018 Oct 1;194:260-267. doi: 10.1016/j.physbeh.2018.06.008. Epub 2018 Jun 7.
• Background Schlahsa L, Jaimes Y, Blasczyk R, Figueiredo C. Granulocyte-colony-stimulatory factor: a strong inhibitor of natural killer cell function. Transfusion. 2011 Feb;51(2):293-305. doi: 10.1111/j.1537-2995.2010.02820.x. Epub 2010 Aug 16.
• Background Smolen JS, Beaulieu A, Rubbert-Roth A, Ramos-Remus C, Rovensky J, Alecock E, Woodworth T, Alten R; OPTION Investigators. Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomised trial. Lancet. 2008 Mar 22;371(9617):987-97. doi: 10.1016/S0140-6736(08)60453-5.
• Background Wild CP, Weiderpass E, Stewart BW, editors. World Cancer Report: Cancer research for cancer prevention. Lyon (FR): International Agency for Research on Cancer; 2020. Available from http://www.ncbi.nlm.nih.gov/books/NBK606505/
• Background Vivier E, Tomasello E, Baratin M, Walzer T, Ugolini S. Functions of natural killer cells. Nat Immunol. 2008 May;9(5):503-10. doi: 10.1038/ni1582.
• Background Wang Y, Jacobs EJ, Gapstur SM, Maliniak ML, Gansler T, McCullough ML, Stevens VL, Patel AV. Recreational Physical Activity in Relation to Prostate Cancer-specific Mortality Among Men with Nonmetastatic Prostate Cancer. Eur Urol. 2017 Dec;72(6):931-939. doi: 10.1016/j.eururo.2017.06.037. Epub 2017 Jul 12.
• Background Weber MM, Michl P, Auernhammer CJ, Engelhardt D. Interleukin-3 and interleukin-6 stimulate cortisol secretion from adult human adrenocortical cells. Endocrinology. 1997 May;138(5):2207-10. doi: 10.1210/endo.138.5.5239.
• Background Wendt K, Wilk E, Buyny S, Buer J, Schmidt RE, Jacobs R. Gene and protein characteristics reflect functional diversity of CD56dim and CD56bright NK cells. J Leukoc Biol. 2006 Dec;80(6):1529-41. doi: 10.1189/jlb.0306191. Epub 2006 Sep 11.
• Background Wu J, Lanier LL. Natural killer cells and cancer. Adv Cancer Res. 2003;90:127-56. doi: 10.1016/s0065-230x(03)90004-2.
• Background Yamada M, Suzuki K, Kudo S, Totsuka M, Nakaji S, Sugawara K. Raised plasma G-CSF and IL-6 after exercise may play a role in neutrophil mobilization into the circulation. J Appl Physiol (1985). 2002 May;92(5):1789-94. doi: 10.1152/japplphysiol.00629.2001.
• Background Zimmer P, Schenk A, Kieven M, Holthaus M, Lehmann J, Lovenich L, Bloch W. Exercise induced alterations in NK-cell cytotoxicity - methodological issues and future perspectives. Exerc Immunol Rev. 2017;23:66-81.
• Background Dorling J, Broom DR, Burns SF, Clayton DJ, Deighton K, James LJ, King JA, Miyashita M, Thackray AE, Batterham RL, Stensel DJ. Acute and Chronic Effects of Exercise on Appetite, Energy Intake, and Appetite-Related Hormones: The Modulating Effect of Adiposity, Sex, and Habitual Physical Activity. Nutrients. 2018 Aug 22;10(9):1140. doi: 10.3390/nu10091140.
• Background Steensberg A, van Hall G, Osada T, Sacchetti M, Saltin B, Klarlund Pedersen B. Production of interleukin-6 in contracting human skeletal muscles can account for the exercise-induced increase in plasma interleukin-6. J Physiol. 2000 Nov 15;529 Pt 1(Pt 1):237-42. doi: 10.1111/j.1469-7793.2000.00237.x.
• Background Dantzer R. Cytokine-induced sickness behavior: mechanisms and implications. Ann N Y Acad Sci. 2001 Mar;933:222-34. doi: 10.1111/j.1749-6632.2001.tb05827.x.
• Background van Gameren MM, Willemse PH, Mulder NH, Limburg PC, Groen HJ, Vellenga E, de Vries EG. Effects of recombinant human interleukin-6 in cancer patients: a phase I-II study. Blood. 1994 Sep 1;84(5):1434-41.
• Background Timper K, Denson JL, Steculorum SM, Heilinger C, Engstrom-Ruud L, Wunderlich CM, Rose-John S, Wunderlich FT, Bruning JC. IL-6 Improves Energy and Glucose Homeostasis in Obesity via Enhanced Central IL-6 trans-Signaling. Cell Rep. 2017 Apr 11;19(2):267-280. doi: 10.1016/j.celrep.2017.03.043.
• Background Lang Lehrskov L, Lyngbaek MP, Soederlund L, Legaard GE, Ehses JA, Heywood SE, Wewer Albrechtsen NJ, Holst JJ, Karstoft K, Pedersen BK, Ellingsgaard H. Interleukin-6 Delays Gastric Emptying in Humans with Direct Effects on Glycemic Control. Cell Metab. 2018 Jun 5;27(6):1201-1211.e3. doi: 10.1016/j.cmet.2018.04.008. Epub 2018 May 3.
• Background Ellingsgaard H, Seelig E, Timper K, Coslovsky M, Soederlund L, Lyngbaek MP, Wewer Albrechtsen NJ, Schmidt-Trucksass A, Hanssen H, Frey WO, Karstoft K, Pedersen BK, Boni-Schnetzler M, Donath MY. GLP-1 secretion is regulated by IL-6 signalling: a randomised, placebo-controlled study. Diabetologia. 2020 Feb;63(2):362-373. doi: 10.1007/s00125-019-05045-y. Epub 2019 Dec 3.
• Background Begg DP, Woods SC. The endocrinology of food intake. Nat Rev Endocrinol. 2013 Oct;9(10):584-97. doi: 10.1038/nrendo.2013.136. Epub 2013 Jul 23.
• Background Medhus AW, Sandstad O, Bredesen J, Husebye E. Delay of gastric emptying by duodenal intubation: sensitive measurement of gastric emptying by the paracetamol absorption test. Aliment Pharmacol Ther. 1999 May;13(5):609-20. doi: 10.1046/j.1365-2036.1999.00519.x.

Drugs

Indications

No indication recorded.