Subscribe to RSS
DOI: 10.1055/a-1186-1009
Resistance Exercise Modulates Kynurenine Pathway in Pancreatic Cancer Patients
Funding: The SUPPORT trial was supported by a grant of the German Caner Aid (Grant No. 110513 and 110552) as well as by additional financial support of the German Cancer Research Center and the University Hospital Heidelberg. Biospecimen storage was further supported by the infrastructure of the NCT Liquid Biobank.![](https://www.thieme-connect.de/media/sportsmed/202101/lookinside/thumbnails/8014_10-1055-a-1186-1009-1.jpg)
Abstract
The aim of this study was to investigate the impact of Supervised and Home-based resistance exercise on the Kynurenine pathway in patients with pancreatic cancer who underwent surgery and chemotherapy. In the SUPPORT study, adult pancreatic cancer patients were randomized to intervention programs of 6-month (1) a Supervised moderate-to-high-intensity progressive resistance training or (2) unsupervised Home-based resistance training, or (3) to a standard care patient Control group. Serum levels of kynurenine, tryptophan and IL-6 were assessed for 32 participants before, after 3 months and after 6 months of exercise intervention. Group differences were investigated using analysis-of-covariance. Patients in the Supervised training group showed decreased levels of serum kynurenine and kynurenine/tryptophan ratio (p = 0.07; p = 0.01 respectively) as well as increased Tryptophan levels (p = 0.05) in comparison to Home-based and Control group over time. The Home-based exercise group had significant increased kynurenine and kynurenine/tryptophan ratio levels. IL-6 levels decreased over the first three months for both intervention groups as well as the Control group (Supervised: p < 0.01, Home-based: p < 0.010, Control group: p < 0.01). Supervised resistance exercise might positively regulate the Kynurenine pathway and downregulate the kynurenine/tryptophan (indicative of IDO/TDO enzyme) levels, hence modulating the immune system.
Publication History
Received: 08 January 2020
Accepted: 14 May 2020
Article published online:
24 July 2020
© 2020. Thieme. All rights reserved.
Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany
-
References
- 1 Talari NK, Panigrahi M, Madigubba S. et al. Altered tryptophan metabolism in human meningioma. J Neurooncol 2016; 130: 69-77
- 2 Campbell BM, Charych E, Lee AW. et al. Kynurenines in CNS disease: Regulation by inflammatory cytokines. Front Neurosci 2014; 8: 12
- 3 Hornyak L, Dobos N, Koncz G. et al. The role of indoleamine-2,3-dioxygenase in cancer development, diagnostics, and therapy. Front Immunol 2018; 9: 151
- 4 Hascitha J, Priya R, Jayavelu S. et al. Analysis of Kynurenine/Tryptophan ratio and expression of IDO1 and 2 mRNA in tumour tissue of cervical cancer patients. Clin Biochem 2016; 49: 919-924
- 5 Eschke RK, Lampit A, Schenk A. et al. Impact of physical exercise on growth and progression of cancer in rodents-a systematic review and meta-analysis. Front Oncol 2019; 9: 35
- 6 Cormie P, Zopf EM, Zhang X. et al. The impact of exercise on cancer mortality, recurrence, and treatment-related adverse effects. Epidemiol Rev 2017; 39: 71-92
- 7 Padilha CS, Testa MT, Marinello PC. et al. Resistance exercise counteracts tumor growth in two carcinoma rodent models. Med Sci Sports Exerc 2019; 51: 2003-2011
- 8 Zimmer P, Joisten N, Schenk A. et al. Impact of physical exercise on the kynurenine pathway in patients with cancer: Current limitations and future perspectives. Acta Oncol 2019; 58: 1116-1117
- 9 Agudelo LZ, Femenia T, Orhan F. et al. Skeletal muscle PGC-1alpha1 modulates kynurenine metabolism and mediates resilience to stress-induced depression. Cell 2014; 159: 33-45
- 10 Millischer V, Erhardt S, Ekblom O. et al. Twelve-week physical exercise does not have a long-lasting effect on kynurenines in plasma of depressed patients. Neuropsychiatr Dis Treat 2017; 13: 967-972
- 11 Allison DJ, Nederveen JP, Snijders T. et al. Exercise training impacts skeletal muscle gene expression related to the kynurenine pathway. Am J Physiol Cell Physiol 2019; 316: C444-C448
- 12 Bansi J, Koliamitra C, Bloch W. et al. Persons with secondary progressive and relapsing remitting multiple sclerosis reveal different responses of tryptophan metabolism to acute endurance exercise and training. J Neuroimmunol 2018; 314: 101-105
- 13 Strasser B, Geiger D, Schauer M. et al. Effects of exhaustive aerobic exercise on tryptophan-kynurenine metabolism in trained athletes. PLoS One 2016; 11: e0153617
- 14 Strasser B, Geiger D, Schauer M. et al. Probiotic supplements beneficially affect tryptophan-kynurenine metabolism and reduce the incidence of upper respiratory tract infections in trained athletes: A randomized, double-blinded, placebo-controlled trial. Nutrients 2016; 8: 752
- 15 O'Leary CB, Hackney AC. Acute and chronic effects of resistance exercise on the testosterone and cortisol responses in obese males: A systematic review. Physiol Res 2014; 63: 693-704
- 16 Pedersen BK, Febbraio MA. Muscle as an endocrine organ: focus on muscle-derived interleukin-6. Physiol Rev 2008; 88: 1379-1406
- 17 Walsh NP, Gleeson M, Shephard RJ. et al. Position statement. Part one: Immune function and exercise. Exerc Immunol Rev 2011; 17: 6-63
- 18 Lewis GD, Farrell L, Wood MJ. et al. Metabolic signatures of exercise in human plasma. Sci Transl Med 2010; 2: 33ra37
- 19 Schlittler M, Goiny M, Agudelo LZ. et al. Endurance exercise increases skeletal muscle kynurenine aminotransferases and plasma kynurenic acid in humans. Am J Physiol Cell Physiol 2016; 310: C836-C840
- 20 Joisten N, Kummerhoff F, Koliamitra C. et al. Exercise and the Kynurenine pathway: Current state of knowledge and results from a randomized cross-over study comparing acute effects of endurance and resistance training. Exerc Immunol Rev 2020; 26: 24-42
- 21 Badawy AA. Kynurenine pathway of tryptophan metabolism: Regulatory and functional aspects. Int J Tryptophan Res 2017; 10: 1178646917691938
- 22 Zimmer P, Schmidt ME, Prentzell MT. et al. Resistance exercise reduces kynurenine pathway metabolites in breast cancer patients undergoing radiotherapy. Front Oncol 2019; 9: 962
- 23 Zhang T, Tan XL, Xu Y. et al. Expression and prognostic value of indoleamine 2,3-dioxygenase in pancreatic cancer. Chin Med J (Engl) 2017; 130: 710-716
- 24 Bahary N, Wang-Gillam A, Haraldsdottir S. et al. Phase 2 trial of the IDO pathway inhibitor indoximod plus gemcitabine / nab-paclitaxel for the treatment of patients with metastatic pancreas cancer. J Clin Oncol 2018; 36: 4015-4015
- 25 Hardee JP, Counts BR, Carson JA. Understanding the role of exercise in cancer cachexia therapy. Am J Lifestyle Med 2019; 13: 46-60
- 26 Wiskemann J, Clauss D, Tjaden C. et al. Progressive resistance training to impact physical fitness and body weight in pancreatic cancer patients: A randomized controlled trial. Pancreas 2019; 48: 257-266
- 27 Padilha CS, Borges FH, Costa Mendes da Silva LE. et al. Resistance exercise attenuates skeletal muscle oxidative stress, systemic pro-inflammatory state, and cachexia in Walker-256 tumor-bearing rats. Appl Physiol Nutr Metab 2017; 42: 916-923
- 28 Harriss DJ, MacSween A, Atkinson G. Ethical standards in sport and exercise science research: 2020 update. Int J Sports Med 2019; 40: 813-817
- 29 Borg G. Perceived Exertion and Pain scales. 1st ed. Champaign: Human Kinetics; 1998
- 30 Clauss D, Tjaden C, Hackert T. et al. Cardiorespiratory fitness and muscle strength in pancreatic cancer patients. Support Care Cancer 2017; 25: 2797-2807
- 31 Qian S, He T, Wang W. et al. Discovery and preliminary structure-activity relationship of 1H-indazoles with promising indoleamine-2,3-dioxygenase 1 (IDO1) inhibition properties. Bioorg Med Chem 2016; 24: 6194-6205
- 32 Lemos H, Huang L, Prendergast GC. et al. Immune control by amino acid catabolism during tumorigenesis and therapy. Nat Rev Cancer 2019; 19: 162-175
- 33 Courneya KS, Friedenreich CM, Quinney HA. et al. A randomized trial of exercise and quality of life in colorectal cancer survivors. Eur J Cancer Care (Engl) 2003; 12: 347-357
- 34 Steins Bisschop CN, Courneya KS, Velthuis MJ. et al. Control group design, contamination and drop-out in exercise oncology trials: A systematic review. PLoS One 2015; 10: e0120996
- 35 Schmidt ME, Meynkohn A, Habermann N. et al. Resistance exercise and inflammation in breast cancer patients undergoing adjuvant radiation therapy: Mediation analysis from a randomized, controlled intervention trial. Int J Radiat Oncol Biol Phys 2016; 94: 329-337
- 36 Fujigaki S, Saito K, Sekikawa K. et al. Lipopolysaccharide induction of indoleamine 2,3-dioxygenase is mediated dominantly by an IFN-gamma-independent mechanism. Eur J Immunol 2001; 31: 2313-2318
- 37 Da Pozzo E, Giacomelli C, Cavallini C. et al. Cytokine secretion responsiveness of lymphomonocytes following cortisol cell exposure: Sex differences. PLoS One 2018; 13: e0200924
- 38 Catena-Dell'Osso M, Bellantuono C, Consoli G. et al. Inflammatory and neurodegenerative pathways in depression: A new avenue for antidepressant development?. Curr Med Chem 2011; 18: 245-255
- 39 Hennings A, Schwarz MJ, Riemer S. et al. Exercise affects symptom severity but not biological measures in depression and somatization - results on IL-6, neopterin, tryptophan, kynurenine and 5-HIAA. Psychiatry Res 2013; 210: 925-933