Effect of 12-Week Low-intensity Exercise on Interleukin-2, Interferon-gamma, and Interleukin-4 Cytokine Production in Rat Spleens Effects of Exercise on Cytokine Production

Main Article Content

Eun-Ju Choi
Chang-Jin Lee
Hyo-Hyun Park
Wi-Young So


exercise, immune system, cytokine production, T helper 1, interferon-gamma


Background and Objective: High-intensity exercise has been linked to immunity; however, the relationship between low-intensity exercise and the immune system is unclear. In this study, the effects of exercise on cytokine production in T helper 1 (interleukin-2 [IL-2] and interferon-gamma [INF-g]) and T helper 2 cells (interleukin-4 [IL-4]) in spleens were investigated.

Material and Methods: Sprague–Dawley male rats were divided into a control group (CON, n = 10) and a low-intensity exercise group (EX, n = 10). EX rats were trained on a treadmill (8 m/min, 50 min/day, 5 times over 12 weeks). Spleen tissues were analyzed by hematoxylin-eosin staining and real-time PCR to quantify IL-4, INF-g, and IL-2 expression.

Results: IL-4 expression was significantly higher in the EX group than in the CON group (p < 0.05). However, IL-2 and INF-g expression did not differ between groups (p > 0.05).

Conclusion: These results suggest that exercise in rats enhances immune function by regulating cytokine production in T helper type 2 (IL-4) cells, but not in T helper type 1 (IL-2 and IFN-g) cells of the activated spleen.

Abstract 347 | pdf Downloads 154


1. Simpson AL, Ray AD, Lundgren CE, et al. Energy cost of breathing at depth: effect of respiratory muscle training. Undersea Hyperbar Med Soc 2012;39(4):829–36.
2. Caris AV, Lira FS, De Mello MT, et al. Carbohydrate and glutamine supplementation modulates the Th1/Th2 balance after exercise performed at a simulated altitude of 4500m. Nutrition 2014;30(11–12):1331–6.
3. Walsh NP, Gleeson M, Shephard RJ, et al. Position statement. Part one: Immune function and exercise. Exercise Immunol Rev 2011;17:6–63.
4. Ryan AS, Nicklas BJ, Berman DM, et al. Adiponectin levels do not change with moderate dietary induced weight loss and exercise in obese postmenopausal women. Int J Obes Relat Meab Disord 2003;27(9):1066–71.
5. Passos GS, Poyares D, Santana MG, et al. Exercise improves immune funtion, antidepressive response, and spleep quality in patients with chronic primary insomnia. BioMed Res Internat 2014;2014:498961.
6. Balkwill F. Cytokines in health and disease. Immunol Today 1993;14(4):149–50.
7. Tanaka S, Inoue S, Isoda F, et al. Impaired immunity in obesity: suppressed but reversible lymphocyte responsiveness. Int J Obesity Relat Metabol Disord 1993;17(11):631–6.
8. Filipov NM, Thompson FN, Sharma RP, et al. Increased proinflammatory cytokine production by ergotamine in male BALB/c mice. J Toxicol Environment Health Part A 1999;58(3):145–55.
9. Gleeson M, Bishop NC, Stensel DJ, et al. The anti-inflammatory effects of exercise: mechanisms and implications for the prevention and treatment of disease. Nature Rev Immunol 2011;11(9):607–15.
10. Collisson E, Griggs L, Drechsler Y. Macrophages from disease resistance B2 haplotype chickens activate T lymphocytes more effectively than macrophages from disease susceptitible B19 birds. Development Comparat Immunol 2017;67:249–56.
11. Mahajan SG, Mehta AA. Suppression of ovalbumin-induced Th2-driven airway inflammation by beta-sitosterol in a guinea pig model of asthma. Eur J Phamacol 2011;650(1):458–64.
12. Li J, Wang J, Shao JQ, et al. Effect of schisandra chinensis on interleukins, glucose metabolism, and pituitary-adrenal and gonadal axis in rats under strenuous swimming exercise. Chinese J Integr Med 2015;21(1):43–8.
13. Kaya O. Effect of a four-week exercise program on the secretion of INF-γ, TNF-γ, IL-2 and IL-6 cytokines in elite Taekwondo athletes. Biosci Rep 2016;5(3):367–70.
14. Ho IC, Miaw SC. Regulation of IL-4 expression in immunity and diseases. Adv Experiment Med Biol 2016;941:31–77.
15. Modabbernia A, Taslimi S, Brietzke E, et al. Cytokine alterations in bipolar disorder: a meta-analysis of 30 studies. Biol Psychiatr 2013;74(1):15–25.
16. Lee H, Baek S, Joe SJ, et al. Modulation of INF-gamma production by TNF-alpha in macrophages from the tumor environment: significance as angiogenic swith. Int Immunopharmacol 2006;6(1):71–8.
17. Cao Y, Hu Y, Zhao HX, et al. Effects of a Chinese traditional formula Kai Xin San (KXS) on chronic fatigue syndrome mice induced by forced wheel running. J Ethnopharmacol 2012;139(1):19–25.
18. Bedford TG, Tipton CM, Wilson NC, et al. Maximum oxygen consumption of rats and its changes with various experimental procedures. J Appl Physiol Respir Environ Exercise Physiol 1979;47(6):1278–83.
19. Choi EJ, Lee S, Chae JR, et al. Eupatilin inhibits lipopolysaccharide-induced expression of inflammatory mediators in macrophages. Life Sci 2011;88(25-26):1121–6.
20. Lee HS, Choi EJ, Lee KS, et al. Oral administration of p-Hydroxycinnamic acid attenuates atopic dermatitis by down regulating Th1 and Th2 cytokine production and keratinocyte activation. PLoS One 2016;11(3):e0150952.
21. Lu YM, Zhang H. Effects of electroacupunture on T-lymphocytes, spleen index, thymus index and lymphopoiesis levels in strenuous exercise-induced stress rats. Zhen Ci Yan Jin 2012;37(2):136–9.
22. Haahr PM, Pedersen BK, Fomsqaard A, et al. Effect of physical exercise on in vitro production of interleukin 1, interleukin 6, tumour necrosis factor-alpha, interleukin 2 and interferon-gamma. Int J Sports Med 1991;12(2):223–7.
23. Kobayashi Y, Nakatsuji A, Aoi W, et al. Intense exercise increases protein oxidation in spleen and liver of mice. Nutr Metab Insights 2014;13(7):1–6.
24. Brubdaker JO, Thompson CM, Morrison LA, et al. Th1-associated immune responses to beta-galactosidase expressed by replication-defective herpes simplex virus. J Immunol 1996;157(4):1598–604.
25. Pisa P, Halapi E, Pisa EK, et al. Selective expresssion of interleukin 10, interferon gamma and granulocyte- macrophage colony-stimulating factor in ovarian cancer biopsies. Proc Nat Acad Sci 1992;89(16):7708–12.
26. Sypek JP, Chung CL, Mayer SH, et al. Resolution for cutaneous leishmaniasis: Interleukin 12 initates a protective T helper type 1 immune response. J Experiment Med 1993;177(6):1797–802.
27. Guo J, Liu C, Wang Y, et al. Role of T hepler lymphokines in the immune-inflammatory pathophysiology of schizophrenia: Systematic review and meta-analysis. Nord J Psychiatr 2015;69(5):364–72.
28. Clerici M, Ferrario E, Trabattoni D, et al. Multiple defects of T helper cell funtion in newly diagnosd patients with Hodgkin’s disease. Eur J Cancer 1994;30(10):1464–70.