Hostname: page-component-586b7cd67f-2brh9 Total loading time: 0 Render date: 2024-11-24T21:08:38.499Z Has data issue: false hasContentIssue false
  • English
  • Français

The role of the cytokine network in psychological stress

Published online by Cambridge University Press:  24 June 2014

Yong-Ku Kim  and
Michael Maes
Yong-Ku Kim*
Affiliation:
Department of Psychiatry, College of Medicine, Korea University, Seoul, Korea
Michael Maes
Affiliation:
Department of Psychiatry and Neuropsychology, Maastricht University, Maastricht, the Netherlands
*
Department of Psychiatry, College of Medicine, Korea University, Ansan Hospital, 516, Go-Jan Dong, Ansan city, Kyunggi Province, 425-020, Korea. Tel: 82-31-412-5140; Fax: 82-31-412-5144; E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

Although a considerable amount of evidence has shown that psychological stress alters peripheral and brain cytokines, the physiological significance of cytokine alteration in psychological stress remains to be elucidated. The aims of this review are to analyze the influence of acute and chronic psychological stresses on the cytokine network in animals and in humans, and to explore the pathophysiological implication of the cytokine changes in psychological stress. Acute psychological stress may increase proinflammatory cytokines both in animals and in humans, and increase T-helper-1 cell cytokines in humans. Investigations into the effect of chronic psychological stress on cytokine production in animals gives mixed results. However, in humans, academic exam stress or care-giver's stress appears to induce a shift in the Th1/Th2 cytokine balance toward a Th2 response and increase proinflammatory cytokines. Psychological stress-induced cytokines stimulate the activity of indoleamine 2,3 dioxygenase (IDO) and could induce serotonin depletion-related disorders such as depression in susceptible individuals. Psychological stress-induced production of cytokines may increase the risk for human diseases, such as cardiovascular disease and exacerbation of autoimmune diseases. Proinflammatory cytokines may also play a regulatory role in glucocorticoid resistance and may be involved in wound healing and skin barrier function alterations. Finally, psychological stress-induced production of cytokines may play a role in neurodegenerative changes in the brain.

Keywords

cytokineinterleukinpsychological stressIDOIRSdepressionschizophrenia
Type
Review Article
Information
Acta Neuropsychiatrica , Volume 15 , Issue 3 , June 2003 , pp. 148 - 155
Copyright
Copyright © 2003 Blackwell Munksgaard

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Espinosa, E, Bermudez-Ruttoni F. Behavior-immunity relationship: the role of cytokines. Rev Invest Clin 2001; 53: 240–253. Google Scholar
Szelenyi, J. Cytokines and the central nervous system. Brain Res Bull 2001;54: 329–338.CrossRefGoogle Scholar
Plata-Salaman, C, Turrin, N. Cytokine interactions and cytokine balance in the brain: relevance to neurology and psychiatry. Mol Psychiatry 1999;4: 302–306. CrossRefGoogle Scholar
Muller, N, Riedel, M, Ackenheil, M, Schwarz, MJ. The role of immune function in schizophrenia: an overview. Eur Arch Psychiatry Clin Neurosci 1999;249(Suppl. 4):62–68.CrossRefGoogle ScholarPubMed
Maes, M. Cytokines in schizophrenia. Biol Psychiatry 1997;42: 308–309.CrossRefGoogle Scholar
Kim, YK, Kim, L, Lee, MS. Relationships between interleukins, neurotransmitters and psychopathology in drug-free male schizophrenics. Schizophr Res 2000;44: 165–175.CrossRefGoogle Scholar
Maes, M. Cytokines in major depression. Biol Psychiatry 1994;36: 498–499.CrossRefGoogle Scholar
Maes, M. Major depression and activation of the inflammatory response system. Adv Exp Med Biol 1999;461: 25–46.CrossRefGoogle Scholar
Maddock, C, Pariante, CM. How does stress affect you? An overview of stress, immunity, depression and disease. Epidemiol Psichiatr Soc 2001;10: 153–162.CrossRefGoogle Scholar
Leonard, BE. The immune system, depression and the action of antidepressants. Prog Neuropsychopharmacol Biol Psychiatry 2001;25: 767–780.CrossRefGoogle Scholar
Kim, YK, Sub, IB, Kim, H, Han, CS, Lim, CS, Choi, Sh, Licinio, J. The plasma levels of interleukin-12 in schizophrenia, major depression, and bipolar mania: effects of psychotropic drugs. Mol Psychiatry 2002;7: 107–114.CrossRefGoogle Scholar
Leonard, BE, Song, C. Stress, depression, and the role of cytokines. Adv Exp Med Biol 1999;461: 251–265.CrossRefGoogle Scholar
Maes, M. Psychological stress, cytokines and the inflammatory response system. Current Opin Psychiatry 1999;12: 695–700. CrossRefGoogle Scholar
Maes, M. Psychological stress and the inflammatory response system. Clin Sci (Lond) 2001;101: 193–194.CrossRefGoogle Scholar
Minami, M, Kuraishi, Y, Yamaguchi, T, Nakai, S, Hirai, Y, Satoh, M. Immobilization stress induces interleukin-1 beta mRNA in the rat hypothalamus. Neurosci Lett 1991;123: 254–256.CrossRefGoogle Scholar
Khlusov, IA, Dygai, AM, Goldberg, ED. The adrenergic regulation of interleukin production by bone marrow cells during immobilization stress. Biull Eksp Biol Med 1993;116: 570–572.Google Scholar
Shintani, F, Nakaki, T, Kanba, S, Kato, R, Asai, M. Role of interleukin-1 in stress responses. A putative neurotransmitter. Mol Neurobiol 1995;10: 47–71.CrossRefGoogle Scholar
Cunnick, JE, Kojic, LD, Hughes, RA. Stress-induced changes in immune function are associated with increased production of an interleukin-1-like factor in young domestic fowl. Brain Behav Immun 1994;8: 123–136.CrossRefGoogle Scholar
Goujon, E, Parnet, P, Laye, S, Combe, C, Kelley, KW, Dantzer, R. Stress downregulates lipopolysaccharide-induced expression of proinflammatory cytokines in the spleen, pituitary, and brain of mice. Brain Behav Immun 1995;9: 292–303.CrossRefGoogle Scholar
Plata-Salaman, CR, Ilyin, SE, Turrin, NPet al. Neither acute nor chronic exposure to a naturalistic (predator) stressor influences the interleukin-1beta system, tumor necrosis factor-alpha, transforming growth factor-beta1, and neuropeptide mRNAs in specific brain regions. Brain Res Bull 2000;51: 187–193.CrossRefGoogle Scholar
Lemay, LG, Vander, AJ, Kluger, MJ. The effects of psychological stress on plasma interleukin-6 activity in rats. Physiol Behav 1990;47: 957–961.CrossRefGoogle Scholar
Soszynski, D, Kozak, W, Conn, CA, Rudolph, K, Kluger, MJ. Beta-adrenoceptor antagonists suppress elevation in body temperature and increase in plasma IL-6 in rats exposed to open field. Neuroendocrinology 1996;63: 459–467.CrossRefGoogle Scholar
Stark, JL, Avitsur, R, Padgett, DA, Campbell, KA, Beck, FM, Sheridan, JF. Social stress induces glucocorticoid resistance in macrophages. Am J Physiol Regul Integr Comp Physiol 2001;280: R1799–1805.Google Scholar
Shizuya, K, Komori, T, Fujiwara, R, Miyahara, S, Ohmori, M, Nomura, J. The influence of restraint stress on the expression of mRNAs for IL-6 and the IL-6 receptor in the hypothalamus and midbrain of the rat. Life Sci 1997;61: PL 135–140.CrossRefGoogle ScholarPubMed
Nukina, H, Sudo, N, Komaki, G, Yu, X, Mine, K, Kubo, C. The restraint stress-induced elevation in plasma interleukin-6 negatively regulates the plasma TNF-alpha level. Neuroimmunomodulation 1998;5: 323–327.CrossRefGoogle Scholar
Ando, T, Rivier, J, Yanaihara, H, Arimura, A. Peripheral corticotropin-releasing factor mediates the elevation of plasma IL-6 by immobilization stress in rats. Am J Physiol 1998;275(5 Part 2):R1461–R1467.Google ScholarPubMed
Takaki, A, Hori, T, Yagi, Set al. Plasma IL-6 and its pyrogenicity during noninflammatory stress. In: Yamashita, H, ed. Control Mechanisms of Stress and Emotion. Amsterdam: Elsevier, 1999: 173–177. Google Scholar
Nukina, H, Sudo, N, Aiba, Y, Oyama, N, Koga, Y, Kubo, C. Restraint stress elevates the plasma interleukin-6 levels in germ-free mice. J Neuroimmunol 2001;115: 46–52.CrossRefGoogle Scholar
Ishikawa, I, Kitamura, H, Kimura, K, Saito, M. Brain interleukin-1 is involved in blood interleukin-6 response to immobilization stress in rats. Jpn J Vet Res 2001;49: 19–25.Google Scholar
Aloe, L, Bracci-Laudiero, L, Alleva, E, Lambiase, A, Micera, A, Tirassa, P. Emotional stress induced by parachute jumping enhances blood nerve growth factor levels and the distribution of nerve growth factor receptors in lymphocytes. Proc Natl Acad Sci USA 1994;91: 10 440–10 444. CrossRefGoogle Scholar
Wu, TC, Xiong, YL, Chen, S, Leng, ST, Hai, T, Tanguay, RM. Biochemical changes of plasma in paratroops after parachuting: a preliminary investigation. Space Med Med Eng (Beijing) 1999;12: 235–239.Google Scholar
Dugue, B, Leppanen, EA, Teppo, AM, Fyhrquist, F, Grasbeck, R. Effects of psychological stress on plasma interleukins-1 beta and 6, C-reactive protein, tumour necrosis factor alpha, anti-diuretic hormone and serum cortisol. Scand J Clin Laboratory Invest 1993;53: 555–561. CrossRefGoogle Scholar
Steptoe, A, Willemsen, G, Owen, N, Flower, L, Mohamed-Ali, V. Acute mental stress elicits delayed increases in circulating inflammatory cytokine levels. Clin Sci (Lond) 2001;101: 185–192.CrossRefGoogle Scholar
Ackerman, KD, Martino, M, Heyman, R, Moyna, NM, Rabin, BS. Stressor-induced alteration of cytokine production in multiple sclerosis patients and controls. Psychosom Med 1998;60: 484–491.CrossRefGoogle Scholar
Goebel, MU, Mills, PJ, Irwin, MR, Ziegler, MG. Interleukin-6 and tumor necrosis factor-alpha production after acute psychological stress, exercise, and infused isoproterenol. differential effects and pathways. Psychosom Med 2000;62: 591–598.CrossRefGoogle Scholar
Larson, MR, Ader, R, Moynihan, JA. Heart rate, neuroendocrine, and immunological reactivity in response to an acute laboratory stressor. Psychosom Med 2001;63: 493–501.CrossRefGoogle Scholar
Mohamed-Ali, V, Bulmer, K, Clarke, D, Goodrick, S, Coppack, SW, Pinkney, JH. Beta-adrenergic regulation of proinflammatory cytokines in humans. Int J Obes Relat Metab Disord 2000;24(Suppl. 2):S154–S155.CrossRefGoogle ScholarPubMed
Gornikiewicz, A, Sautner, T, Brostjan, Cet al. Catecholamines up-regulate lipopolysaccharide-induced IL-6 production in human microvascular endothelial cells. FASEB J 2000;14: 1093–1100.Google Scholar
Kubera, M, Symbirtsev, A, Basta-Kaim, Aet al. Effect of chronic treatment with imipramine on interleukin 1 and interleukin 2 production by splenocytes obtained from rats subjected to a chronic mild stress model of depression. Pol J Pharmacol 1996;48: 503–506.Google Scholar
Mekaouche, M, Givalois, L, Barbanel, Get al. Chronic restraint enhances interleukin-1-beta release in the basal state and after an endotoxin challenge, independently of adrenocorticotropin and corticosterone release. Neuroimmunomodulation 1994;1: 292–299.CrossRefGoogle Scholar
McCarthy, DO, Ouimet, ME, Daun, JM. The effects of noise stress on leukocyte function in rats. Res Nurs Health 1992;15: 131–137.CrossRefGoogle Scholar
Batuman, OA, Sajewski, D, Ottenweller, JE, Pitman, DL, Natelson, Bh. Effects of repeated stress on T cell numbers and function in rats. Brain Behav Immun 1990;4: 105–117.CrossRefGoogle Scholar
Marshall, GD Jr,Agarwal, SK, Lloyd, C, Cohen, L, Henninger, EM, Morris, GJ. Cytokine dysregulation associated with exam stress in healthy medical students. Brain Behav Immun 1998;12: 297–307.CrossRefGoogle Scholar
Guidi, L, Tricerri, A, Vangeli, Met al. Neuropeptide Y plasma levels and immunological changes during academic stress. Neuropsychobiology 1999;40: 188–195.CrossRefGoogle Scholar
Paik, Ih, Toh, KY, Lee, C, Kim, JJ, Lee, SJ. Psychological stress may induce increased humoral and decreased cellular immunity. Behav Med 2000;26: 139–141.CrossRefGoogle Scholar
Kang, Dh, Fox, C. Th1 and Th2 cytokine responses to academic stress. Res Nurs Health 2001;24: 245–257.CrossRefGoogle Scholar
Maes, M, Song, C, Lin, Aet al. The effects of psychological stress on humans: increased production of pro-inflammatory cytokines and a Th1-like response in stress-induced anxiety. Cytokine 1998;10: 313–318.CrossRefGoogle Scholar
Glaser, R, Rice, J, Speicher, CE, Stout, JC, Kiecolt-Glaser, JK. Stress depresses interferon production by leukocytes concomitant with a decrease in natural killer cell activity. Behav Neurosci 1986;100: 675–678.CrossRefGoogle Scholar
Song, C, Kenis, G, Van Gastel, Aet al. Influence of psychological stress on immune-inflammatory variables in normal humans. Part II. Altered serum concentrations of natural anti-inflammatory agents and soluble membrane antigens of monocytes and T lymphocytes. Psychiatry Res 1999;85: 293–303.CrossRefGoogle Scholar
Kiecolt-Glaser, JK, Marucha, PT, Malarkey, WB, Mercado, AM, Glaser, R. Slowing of wound healing by psychological stress. Lancet 1995;346: 1194–1196.CrossRefGoogle Scholar
Kiecolt-Glaser, JK, Glaser, R, Gravenstein, S, Malarkey, WB, Sheridan, J. Chronic stress alters the immune response to influenza virus vaccine in older adults. Proc Natl Acad Sci USA 1996;93: 3043–3047.CrossRefGoogle Scholar
Lutgendorf, SK, Garand, L, Buckwalter, KC, Reimer, TT, Hong, SY, Lubaroff, DM. Life stress, mood disturbance, and elevated interleukin-6 in healthy older women. J Gerontol a Biol Sci Med Sci 1999;54: M434–M439.CrossRefGoogle Scholar
Glaser, R, MacCallum, RC, Laskowski, BF, Malarkey, WB, Sheridan, JF, Kiecolt-Glaser, JK. Evidence for a shift in the Th-1 to Th-2 cytokine response associated with chronic stress and aging. J Gerontol a Biol Sci Med Sci 2001;56: M477–M482.CrossRefGoogle Scholar
Licinio, J, Wong, ML. The role of inflammatory mediators in the biology of major depression. central nervous system cytokines modulate the biological substrate of depressive symptoms, regulate stress-responsive systems, and contribute to neurotoxicity and neuroprotection. Mol Psychiatry 1999;4: 317–327.CrossRefGoogle Scholar
Maes, M. Interleukin-1beta and the etiology of depression. Acta Psychiatr Scand 2001;103: 161–162.Google Scholar
Leonard, BE. Changes in the immune system in depression and dementia: causal or co-incidental effects? Int J Dev Neurosci 2001;19: 305–312.CrossRefGoogle Scholar
Guillemin, GJ, Kerr, SJ, Pemberton, LA, Smith, DG, Smythe, GA, Armati, PJ, Brew, BJ. IFN-beta1b induces kynurenine pathway metabolism in human macrophages: potential implications for multiple sclerosis treatment. J Interferon Cytokine Res 2001;21: 1097–1101.CrossRefGoogle Scholar
Sakash, JB, Byrne, GI, Lichtman, A, Libby, P. Cytokines induce indoleamine 2,3-dioxygenase expression in human atheroma-associated cells: implications for persistent Chlamydophila pneumoniae infection. Infect Immun 2002;70: 3959–3961.CrossRefGoogle Scholar
Capuron, L, Ravaud, A, Neveu, PJ, Miller, Ah, Maes, M, Dantzer, R. Association between decreased serum tryptophan concentrations and depressive symptoms in cancer patients undergoing cytokine therapy. Mol Psychiatry 2002;7: 468–473.CrossRefGoogle Scholar
Meltzer, HY. Role of serotonin in depression. Ann NY Acad Sci 1990;600: 486–499.CrossRefGoogle Scholar
Ridker, PM, Rifai, N, Stampfer, MJ, Hennekens, Ch. Plasma concentration of interleukin-6 and the risk of future myocardial infarction among apparently healthy men. Circulation 2000;101: 1767–1772.CrossRefGoogle Scholar
Ridker, PM, Rifai, N, Pfeffer, M, Sacks, F, Lepage, S, Braunwald, E. Elevation of tumor necrosis factor-alpha and increased risk of recurrent coronary events after myocardial infarction. Circulation 2000;101: 2149–2153.CrossRefGoogle Scholar
Biasucci, LM, Liuzzo, G, Fantuzzi, Get al. Increasing levels of interleukin (IL)-1Ra and IL-6 during the first 2 days of hospitalization in unstable angina are associated with increased risk of in-hospital coronary events. Circulation 1999;99: 2079–2084.CrossRefGoogle Scholar
Ross, R. Atherosclerosis is an inflammatory disease. Am Heart J 1999;138: S419–S420.CrossRefGoogle Scholar
Yudkin, JS, Kumari, M, Humphries, SE, Mohamed-Ali, V. Inflammation, obesity, stress and coronary heart disease: is interleukin-6 the link? Atherosclerosis 2000;148: 209–214.CrossRefGoogle Scholar
Appels, A, Bar, FW, Bar, J, Bruggeman, C, De Baets, M. Inflammation, depressive symptomtology, and coronary artery disease. Psychosom Med 2000;62: 601–605.CrossRefGoogle Scholar
Hirano, D, Nagashima, M, Ogawa, R, Yoshino, S. Serum levels of interleukin 6 and stress related substances indicate mental stress condition in patients with rheumatoid arthritis. J Rheumatol 2001;28: 490–495.Google Scholar
Jacobs, R, Pawlak, CR, Mikeska, Eet al. Systemic lupus erythematosus and rheumatoid arthritis patients differ from healthy controls in their cytokine pattern after stress exposure. Rheumatology (Oxford) 2001;40: 868–875.CrossRefGoogle Scholar
Schmid-Ott, G, Jaeger, B, Meyer, S, Stephan, E, Kapp, A, Werfel, T. Different expression of cytokine and membrane molecules by circulating lymphocytes on acute mental stress in patients with atopic dermatitis in comparison with healthy controls. J Allergy Clin Immunol 2001;108: 455–462.CrossRefGoogle Scholar
Deinzer, R, Forster, P, Fuck, L, Herforth, A, Stiller-Winkler, R, Idel, H. Increase of crevicular interleukin 1beta under academic stress at experimental gingivitis sites and at sites of perfect oral hygiene. J Clin Periodontol 1999;26: 1–8.CrossRefGoogle Scholar
Quan, N, Avitsur, R, Stark, JLet al. Social stress increases the susceptibility to endotoxic shock. J Neuroimmunol 2001;115: 36–45.CrossRefGoogle Scholar
Avitsur, R, Stark, JL, Dhabhar, FS, Padgett, DA, Sheridan, JF. Social disruption-induced glucocorticoid resistance: kinetics and site specificity. J Neuroimmunol 2002;124: 54–61.CrossRefGoogle Scholar
Avitsur, R, Stark, JL, Sheridan, JF. Social stress induces glucocorticoid resistance in subordinate animals. Horm Behav 2001;39: 247–257.CrossRefGoogle Scholar
Stark, JL, Avitsur, R, Hunzeker, J, Padgett, DA, Sheridan, JF. Interleukin-6 and the development of social disruption-induced glucocorticoid resistance. J Neuroimmunol 2002;124: 9–15.CrossRefGoogle Scholar
Marucha, PT, Kiecolt-Glaser, JK, Favagehi, M. Mucosal wound healing is impaired by examination stress. Psychosom Med 1998;60: 362–365.CrossRefGoogle Scholar
Glaser, R, Kiecolt-Glaser, JK, Marucha, PT, MacCallum, RC, Laskowski, BF, Malarkey, WB. Stress-related changes in proinflammatory cytokine production in wounds. Arch General Psychiatry 1999;56: 450–456. CrossRefGoogle Scholar
Mercado, AM, Padgett, DA, Sheridan, JF, Marucha, PT. Altered kinetics of IL-1 alpha, IL-1 beta, and KGF-1 gene expression in early wounds of restrained mice. Brain Behav Immun 2002;16: 150–162.CrossRefGoogle Scholar
Altemus, M, Rao, B, Dhabhar, FS, Ding, W, Granstein, RD. Stress-induced changes in skin barrier function in healthy women. J Invest Dermatol 2001;117: 309–317.CrossRefGoogle Scholar
Oka, T, Oka, K, Hori, T. Mechanisms and mediators of psychological stress-induced rise in core temperature. Psychosom Med 2001;63: 476–486.CrossRefGoogle Scholar
Mark, KS, Trickler, WJ, Miller, DW. Tumor necrosis factor-alpha induces cyclooxygenase-2 expression and prostaglandin release in brain microvessel endothelial cells. J Pharmacol Exp Ther 2001;297: 1051–1058.Google Scholar
Allan, SM, Rothwell, NJ. Cytokines and acute neurodegeneration. Nat Rev Neurosci 2001;2: 734–744.CrossRefGoogle Scholar
Madrigal, JL, Hurtado, O, Moro, MAet al. The increase in TNF-alpha levels is implicated in NF-kappaB activation and inducible nitric oxide synthase expression in brain cortex after immobilization stress. Neuropsychopharmacology 2002;26: 155–163.CrossRefGoogle Scholar