CORTISOL LEVEL AND DYNAMICS OF BEHAVIORAL REACTIONS IN MICE UNDER THE INFLUENCE OF INTERLEUKIN-2 DURING PHYSICAL TRAINING

Authors

DOI:

https://doi.org/10.11603/bmbr.2706-6290.2021.2.11942

Keywords:

stress hormone, behavioral activity, physical activity, adaptation, cytokine

Abstract

Summary. The reaction of the hypothalamic-pituitary-adrenal system, accompanied by an increase in blood cortisol, adequate to the amount of exercise, can serve as an important early indicator of overtraining and stress. Stress, in turn, leads to significant changes in the central nervous system, which is clearly manifested in behavioral reactions. Interleukin-2 (IL-2) may have a simultaneous effect on the regulation of homeostasis in the brain and immune system. The drug IL-2 is effectively used in the treatment of immunosuppression caused by stress, and has stimulating and antidepressant effects.

The aim of the study – to evaluate the effect of IL-2 on cortisol levels and the dynamics of behavioral responses in mice under physical stress.

Materials and Methods. The study was performed on adult male laboratory mice. Five experimental and one control (without physical training) groups of animals were formed. Group I received an inhibitor of IL-2 (Cyclosporine) (10 mg/kg), groups II, III and IV – IL-2 (Roncoleukin) in concentrations of 5000, 7500 and 30,000 IU/kg, respectively, group V – sterile saline. The method of forced swimming to complete exhaustion with a load was used as physical training. The content of cortisol in the blood serum was determined using reagents "Cortisol – ELISA". The behavior of animals was studied using the method of “Open field”.

Results. Stimulation of IL-2 in high concentrations led to a significant increase in serum cortisol levels in mice at 4 and 6 weeks compared to the control and previous period (p≤0.05). Animals administered IL-2 at medium concentrations had a moderate increase in cortisol levels, which increased during all phases of adaptation to exercise. Significant differences were observed compared with the control (respectively, by 51.8 % – at the 4th, by 36.5 % – at the 6th week, p≤0.05). In the group of animals with IL-2 inhibition, cortisol levels at week 4 decreased compared to the previous period (by 16 %, p≤0.05) with a subsequent significant increase (by 110 %, p≤0.05). Groups of animals with low-concentration IL-2 stimulation and no drug exposure showed an increase in cortisol levels compared to controls at week 4 and compared to previous values at week 6 of exercise. During all periods of the experiment, there was a difference in behavioral activity in the “Open field” test depending on the period and the effect of IL-2 of different concentrations or its inhibition.

Conclusions. It was found that the introduction of IL-2 affects the concentration of cortisol in the serum of laboratory mice that were exposed to exercise. Animals administered IL-2 at medium concentrations did not have a significant increase in cortisol levels. At low concentrations of IL-2, cortisol levels increased with a significant decrease in the recovery phase. Under conditions of high concentrations of IL-2, cortisol levels increased during all weeks, with a significant jump in the last week of exercise. Therefore, average concentrations of IL-2 have a stress-protective effect under exercise. In a model of physical stress in white mice, it was shown that the introduction of IL-2 affects the behavior of experimental animals. At medium concentrations, IL-2 leads to a decrease in anxiety, increased motor activity of animals and increased research behavior.

References

Meerson FZ, Pshennikova MG. Adaptation to stressful situations and physical loads. [Адаптация к стрессорным ситуациям и физическим загрузкам] Мoscow: Meditsina, 1988. Russian.

Kozlov VA, Kudaeva OT. [Immune system and exercise]. Meditsinskaya immunologiya. 2002;4(3): 427-38. Russian.

Gleeson M. Immune function in sport and exercise. J Appl Physiol. 2007;103: 693-9.

Nieman DC, Wentz LM. The compelling link between physical activity and the body's defense system. J Sport Health Sci. 2019;8(3): 201-17. DOI: 10.1016/j.jshs.2018.09.009

Wang J, Liu Sh, Li G, Xiao J. Exercise regulates the immune system. Adv Exp Med Biol. 2020;1228: 395-408. DOI: 10.1007/978-981-15-1792-1_27

Gonçalves CAM, Dantas PMS, Santos IKD, Dantas M, da Silva DCP, Tinoco Cabral BrG, et al. Effect of acute and chronic aerobic exercise on immunological markers: a systematic review. Front Physiol. 2019;10: 1602. DOI: 10.3389/fphys.2019.01602

Hackney AC. Stress and the neuroendocrine system: the role of exercise as a stressor and modifier of stress. Expert Rev Endocrinol Metab. 2006;1(6): 783-92. DOI: 10.1586/17446651.1.6.783

Buresh Ya, Bureshova О, Khyuston JP. Techniques and basic experiments to study the brain and behavior. [Методики и основные эксперименты по изучению мозга и поведения] Мoscow: Vysshaya shkola; 1991. Russian.

Shvets V, Shkuropat A, Prosiannikova Y, Golovchenko I. Effect of interleukin-2 on the humoral link of immunity during physical activity. Journal of Physical Education and Sport. 2020;20(Suppl issue 6): 3153-9. DOI: 10.7752/jpes.2020.s6427

Pinto RA, Arredondo SM, Bono MR, Gaggero AA, Díaz PV. T helper 1/T helper 2 cytokine imbalance in respiratory syncytial virus infection is associated with increased endogenous plasma cortisol. Pediatrics. 2006;117(5): e878-86. DOI: 10.1542/peds.2005-2119

Suzuki K, Harumi H. Effect of exercise intensity on cell-mediated immunity. Sports (Basel). 2021;9(1): 8. DOI: 10.3390/sports9010008

Rankin JS, Zalcman SS, Zhu Y, Siegel A. Short- and long-term effects of interleukin-2 treatment on the sensitivity of periadolescent female mice to interleukin-2 and dopamine uptake inhibitor. PLoS ONE. 2013;8(5): e64473. DOI: 10.1371/journal.pone.0064473

Waters RS, Perry JSA, Han SP, Bielekova B, Gedeon T. The effects of interleukin-2 on immune response regulation. Math Med Biol. 2018;35(1): 79-119. DOI: 10.1093/imammb/dqw021

Ross SH, Cantrell DA. Signaling and function of interleukin-2 in T lymphocytes. Annu Rev Immunol. 2018;36: 411-33. DOI: 10.1146/annurev-immunol-042617-053352

Petitto JM, Meola D, Huang Z. Interleukin-2 and the brain: dissecting central versus peripheral contributions using unique mouse models. Methods Mol. Biol. 2012;934: 301-11. DOI: 10.1007/978-1-62703-071-7_15

Klatzmann D, Abbas AK. The promise of low-dose interleukin-2 therapy for autoimmune and inflammatory diseases. Nat Rev Immunol. 2015;15(5): 283-94. DOI: 10.1038/nri3823

Alves S, Churlaud G, Audrain M, Michaelsen-Preusse K, Fol R, Souchet B, et al. Interleukin-2 improves amyloid pathology, synaptic failure and memory in Alzheimer's disease mice. Brain. 2017;140(3): 826-42. DOI: 10.1093/brain/aww330

Shurlygina AV, Galiamina AG, Melnikova EV, Panteleeva NG, Tenditnik MV, Trufakin VA, et al. Effects of roncoleukin on immune parameters and mixed anxiety/depression state induced by chronic social defeat stress in male mice. Ross Fiziol Zh Im IM Sechenova. 2014;100(2): 201-14.

Gong S., Miao Y-L, Jiao G-Zh, Sun M-J, Li H, Lin J, et al. Dynamics and correlation of serum cortisol and corticosterone under different physiological or stressful conditions in mice. PLoSONE. 2015;10(2): e0117503. DOI: 10.1371/journal.pone.0117503

Rutherfurd-Markwick K, Starck C, Dulson DK, Ali A. Salivary diagnostic markers in males and females during rest and exercise. J Int Soc Sports Nutr. 2017;14: 27. DOI: 10.1186/s12970-017-0185-8

Suzdalnitskiy RS, Levando VA. [New approaches to understanding sports stress immunodeficiencies] Teoriya i praktika fiz. kultury. 2003;1: 18-22. Russian.

Roelfsema F, Peter YL, Yang R, Takahashi P, Veldhuis JD Interleukin-2 drives cortisol secretion in an age-, dose-, and body composition-dependent way. Endocr Connect. 2020;9(7): 637-48. DOI: 10.1530/EC-20-0211

Published

2021-09-02

How to Cite

Shvets, V. A., & Hasiuk, O. M. (2021). CORTISOL LEVEL AND DYNAMICS OF BEHAVIORAL REACTIONS IN MICE UNDER THE INFLUENCE OF INTERLEUKIN-2 DURING PHYSICAL TRAINING. Bulletin of Medical and Biological Research, (2), 95–102. https://doi.org/10.11603/bmbr.2706-6290.2021.2.11942