Role of opioid receptors in phagocytosis regulation and production of Th1/Th2 cytokines under acute cold stress in non-immune mice

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Abstract

Endogenous opioid system plays an important role in the regulation of body functions under stress, providing stress-protective, analgesic and immunoregulatory effects. The aim of this work was to assess the effect of acute cold stress on the in vivo production of adaptive immunity cytokines IL-2, IL-4, IFNγ, phagocytosis, and production of reactive oxygen species in non-immunized mice with induced blockage of opioid receptors. The object of the study were male white mice subjected to acute cold stress at -20 °C for 10 or 60 minutes. To block opioid receptors, naloxone hydrochloride was used, which was administered subcutaneously at a dose of 0.2 mg/kg 20 min before inducing the stress. After the cold exposure, spleen and peritoneal lavage were obtained from the animals. The cytokine concentrations were determined using ELISA technique. The absorption activity of CD11+ cells of the peritoneal cavity was assessed using FITC-stained St.cohnii with a flow cytometer; the production of reactive oxygen species was assessed using the reaction of luminol-dependent chemiluminescence.

It was found that the both cold stress regimens caused naloxone-independent inhibition of spontaneous IFNγ production. In stimulated cultures, an inhibitory effect on IFNγ secretion was registered in animals subjected to stress for only 60 min, being also independent on the opioid receptor blockade. IL-2 production decreased in stimulated cultures against the background of 60 min stress naloxone independently. Both variants of cold stress had no effect on IL-4 production. Stress for 60 min inhibited absorption activity of CD11+ cells from the peritoneal lavage and activated production of oxygen radicals, being, however, canceled by naloxone administration. Hence, acute cold stress led to naloxone-independent inhibition of Th1 cytokine production by splenocytes, naloxone-dependent inhibition of phagocytosis and activation of the microbicidal potential of peritoneal cavity cells.

About the authors

Sergey V. Gein

Institute of Ecology and Genetics of Microorganisms, Perm Federal Research Center, Ural Branch, Russian Academy of Sciences; Perm State University

Author for correspondence.
Email: gein@iegm.ru
ORCID iD: 0000-0002-0799-3397
SPIN-code: 2323-9572

PhD, MD (Medicine), Professor, Department of Microbiology and Immunology, Perm State National Research University; Director, Institute of Ecology and Genetics of Microorganisms, Perm Federal Research Center, Ural Branch, Russian Academy of Sciences

Russian Federation, Perm; Perm

I. L. Sharavieva

Institute of Ecology and Genetics of Microorganisms, Perm Federal Research Center, Ural Branch, Russian Academy of Sciences

Email: irin.sh@gmail.com

PhD (Biology), Research Associate, Laboratory of Developmental Biochemistry of Microorganisms

Russian Federation, Perm

References

  1. Гейн С.В., Баева Т.А., Гейн О.Н., Черешнев В.А. Роль моноцитов в реализации эффектов β-эндорфина и селективных агонистов µ- и δ-опиатных рецепторов на пролиферативную активность лимфоцитов периферической крови // Физиология человека, 2006. Т. 32, № 3. С 111-116. [Gein S.V., Baeva T.A., Gein O.N., Chereshnev V.A. The role of monocytes in the effects of beta-endorphin and selective agonists of mu- and delta-Opiate receptors on the proliferative activity of peripheral blood lymphocytes. Fiziologiya cheloveka = Human Physiology, 2006, Vol. 32, no. 3, pp. 111-116. (In Russ.)]
  2. Гейн С.В., Брагина Н.А., Шаравьева И.Л. Влияние стресса на антителогенез, продукцию IL-2, IL-4, IFN-γ в зависимости от времени введения антигена и оценка роли опиоидных рецепторов // Бюллетень экспериментальной биологии и медицины, 2023. Т. 175. № 3. С. 298-304. [Gein S.V., Bragina N.A., Sharav’eva I.L. Effect of stress on the production of antibodies and IL-2, IL-4, IFNγ depending on the time of antigen administration and evaluation of the role of opioid receptors. Byulleten eksperimentalnoy biologii i meditsiny = Bulletin of Experimental Biology and Medicine, 2023, Vol. 175, no. 3, pp. 298-304. (In Russ.)]
  3. Гейн С.В., Кадочникова Я.А. Влияние эндоморфинов-1,2 на функциональную активность нейтрофилов и моноцитов периферической крови in vitro // Физиология человека, 2021. Т. 47, № 6. С. 65-71. [Gein S.V., Kadochnikova Y.A. Effect of endomorphins-1, 2 on functional activity of neutrophils and peripheral blood monocytes in vitro. Fiziologiya cheloveka = Human Physiology, 2021, Vol. 47, no. 6, pp. 65-71. (In Russ.)]
  4. Гейн С.В., Шаравьева И.Л. Влияние холодового стресса на функциональную активность перитонеальных макрофагов мыши в условиях блокады опиатных рецепторов // Российский физиологический журнал им. Сеченова, 2016. Т. 102, № 2. С. 188-194. [Gein S.V., and Sharav’eva I.L. Effects of cold stress on the functional activity of mouse peritoneal macrophages in conditions of opiate receptor. Rossiiskii fiziologicheskii zhurnal imeni I.M. Sechenova = I. Sechenov Russian Physiological Journal, 2016, Vol. 102, no. 2, pp. 188-194. (In Russ.)]
  5. Макарова О.В., Трунова Г.В., Диатроптов М.Е., Серебряков С.Н., Кондашевская М.В., Малайцев В.В. Сравнительная характеристика продукции цитокинов активированными конканавалином А спленоцитами мышей BALB/C и С57В1/6 при холодовом воздействии // Бюллетень экспериментальной биологии и медицины, 2005. Т. 139, № 2. С. 188- 190. [Makarova. O.V., Trunova G.V., Diatroptov M.E., Serebryakov S.N., Kondashevskaya M.V., Malaitsev V.V. Comparative characterization of cytokine production by concanavalin A-activated splenocytes from BALB/c and C57BL/6 mice after cold exposure. Byulleten eksperimentalnoy biologii i meditsiny = Bulletin of Experimental Biology and Medicine, 2005, Vol. 139, no. 2, pp. 188-190. (In Russ.)]
  6. Aviles H., Johnson M.T., Monroy F.P. Effects of cold stress on spleen cell proliferation and cytokine production during chronic Toxoplasma gondii infection. Neuroimmunomodulation, 2004, Vol. 11, pp. 93-102.
  7. Bali A., Randhawa P. K., Jaggi A. S. Stress and opioids: Role of opioids in modulating stress-related behavior and effect of stress on morphine conditioned place preference. Neurosci. Biobehav. Rev., 2015, Vol. 51, pp. 138-150.
  8. Banerjee S.K., Aviles H., Fox M.T., Monroy F.P. Cold stress-induced modulation of cell immunity during acute Toxoplasma gondii infection in mice. J. Parasitol., 1999, Vol. 85, no. 3, pp. 442-447.
  9. Hangalapura B.N., Kaiser M.G., Poel J.J., Parmentier H.K., Lamont S. Cold stress equally enhances in vivo pro-inflammatory cytokine gene expression in chicken lines divergently selected for antibody responses. Dev. Comp. Immunol., 2006, Vol. 30, pp. 503-511.
  10. Manglik A., Kruse A.C., Kobilka T.S., Thian F.S., Mathiesen J.M., Sunahara R.K., Pardo L., Weis W.I., Kobilka B.K., Granier S. Crystal structure of the µ-opioid receptor bound to a morphinan antagonist. Nature, 2012, Vol. 485, pp. 321-326.
  11. McEwen B.S., Biron C.A., Brunson K.W., Bulloch K., Chambers W.H., Dhabhar F.S., Goldfarb R.H., Kitson R.P., Miller A.H., Spencer R.L., Weiss. J.M. The role of adrenocorticoids as modulators of immune function in health and disease: neural, endocrine and immune interactions. Brain Res. Brain Res. Rev., 1997, Vol. 23, pp. 79-133.
  12. Palermo-Neto J., de Oliveira Massoco C., Robespierre de Souza W. Effects of physical and psychological stressors on behavior, macrophage activity, and Ehrlich tumor growth. Brain Behav. Immun., 2003, Vol. 17 no. 1, pp. 43-54.
  13. Shevchuk N.A., Radoja S. Possible stimulation of anti-tumor immunity using repeated cold stress: a hypothesis. Infect. Agent Cancer, 2007, Vol. 2, no. 20, pp. 1-9.
  14. Smith E.M. Neuropeptides as signal molecules in common with leukocytes and the hypothalamic-pituitary-adrenal axis. Brain Behav. Immun., 2008, Vol. 22, no. 1, pp. 3-14.
  15. Vaswani K.K., Richard C.W., Tejwani G.A. Cold swim stress-induced changes in the levels of opioid peptides in the rat CNS and peripheral tissues. Pharmacol. Biochem. Behav., 1988, Vol. 29, no. 1, pp. 163-168.
  16. Vialard F., Olivier M. Thermoneutrality and immunity: how does cold stress affect disease? Front. Immunol., 2020, Vol. 11, 588387. doi: 10.3389/fimmu.2020.588387.
  17. Willemsen G., Carroll D., Ring C., Drayson M. Cellular and mucosal immune reactions to mental and cold stress: associations with gender and cardiovascular reactivity. Psychophysiology, 2002, Vol. 39, no. 3, pp. 222-228.
  18. Zhang Z., Chen B., Yuan L., Niu C. Acute cold stress improved the transcription of pro-inflammatory cytokines of Chinese soft-shelled turtle against Aeromonas hydrophila. Dev. Comp. Immunol., 2015, Vol. 49, no. 1, pp. 127-137.
  19. Zhao F.Q., Zhang Z.W., Qu J.P., Yao H.D., Li M., Li S., Xu S.W. Cold stress induces antioxidants and Hsps in chicken immune organs. Cell Stress Chaperones, 2014, Vol. 19, pp. 635-648.

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2. Figure 1. Effect of 10 min (A) and 60 min (B) cold stress on spontaneous and stimulated production of IFNγ by mouse splenocytes under conditions of blockade of opiate receptors

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3. Figure 2. Effect of 10 min (A) and 60 min (B) cold stress on spontaneous and stimulated production of IL-2 by mouse splenocytes under conditions of blockade of opiate receptors

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4. Figure 3. Effect of 10 min (A) and 60 min (B) cold stress on spontaneous and stimulated production of IL-4 by mouse splenocytes under conditions of blockade of opiate receptors

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5. Figure 4. Influence of 10 min and 60 min cold stress on the phagocytosis of CD11+ mouse peritoneal lavage cells under conditions of blockade of opiate receptors

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6. Figure 5. Effects of 10 min (A) and 60 min (B) cold stress on stimulated ROS production by mouse peritoneal cells under conditions of blockade of opiate receptors

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Copyright (c) 2024 Gein S.V., Sharavieva I.L.

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