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Stressor-induced modulation of immune function: a review of acute, chronic effects in animals

Published online by Cambridge University Press:  24 June 2014

Alexander W. Kusnecov  and
Alba Rossi-George
Alexander W. Kusnecov*
Affiliation:
Department of Psychology, Rutgers, State University of New Jersey, Piscataway, New Jersey, USA
Alba Rossi-George
Affiliation:
Department of Psychology, Rutgers, State University of New Jersey, Piscataway, New Jersey, USA
*
Alexander W. Kusnecov, Department of Psychology, Biopsychology and Behavioral Neuroscience Program, Rutgers, State University of New Jersey, 152 Frelinghuysen Road, Piscataway, NJ, USA; Tel: + (732) 445 3473; Fax: + (732) 445 2263; E-mail: [email protected]
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Abstract

The present paper reviews recent studies on the effects of stress on immune function in laboratory animals. The emphasis is on those studies where a simultaneous comparison of acute and chronic stress regimens was determined, although additional relevant studies are also reviewed. The effects of stress on basic measurements of cellular and humoral immune measures are discussed, including the growing number of studies that have reported alterations in macrophage functions. The latter are key elements in the innate immune response, and like measurements of T cell function and antibody production, are inhibited and enhanced by stressor exposure. This review does not focus on the mechanisms by which stress alters immune function, there being little to add conceptually in terms of what was reported previously (see Kusnecov AW, Rabin BS, Int Arch Allergy Immunol 1994;105:107–121.). However, a question is raised in the conclusion as to how stressor effects on immune function should be interpreted, for it is clear that immunological processes in and of themselves elicit central nervous system responses that neurochemically and endocrinologically do not differ from those produced in response to psychological stressors. Therefore, at least in the short term stressor-induced immune changes may not necessarily reflect maladaptive adjustments, although, as demonstrated by some studies reviewed in this paper, they may pose a serious risk to health should stressor exposure be persistent and uncontrolled.

Keywords

psychoneuroimmunologystresshumoral immunitycellular immunitymacrophagesB cellsT cellsantibodycytokinesratsmice
Type
Review Article
Information
Acta Neuropsychiatrica , Volume 14 , Issue 6 , December 2002 , pp. 279 - 291
Copyright
Copyright © Acta Neuropsychiatrica 2002

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References

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 ScholarPubMed
Licinio, J. Central nervous system cytokines and their relevance for neurotoxicity and apoptosis. J Neural Transm Suppl 1997;49: 169–175.Google ScholarPubMed
Matzinger, P. Tolerance, danger, and the extended family. Ann Revimmunol 1994;12: 991–1045. Google ScholarPubMed
Vance, RE. Cutting edge commentary: a Copernican revolution? Doubts about the danger theory. J Immunol 2000;165: 1725–1728.CrossRefGoogle ScholarPubMed
Schwartz, M. T cell mediated neuroprotection is a physiological response to central nervous system insults. J Mol Med 2001;78: 594–597.CrossRefGoogle ScholarPubMed
Levite, M. Neuropeptides, by direct interaction with T cells, induce cytokine secretion and break the commitment to a distinct T helper phenotype. Proc Natl Acad Sci USA 1998;95: 12544–12549.CrossRefGoogle Scholar
Kiecolt-Glaser, JK, McGuire, L, Robles, TF, Glaser, R. Psychoneuroimmunology and psychosomatic medicine: back to the future. Psychosom Med 2002;64: 15–28.CrossRefGoogle ScholarPubMed
Cohen, S, Miller, GE, Rabin, BS. Psychological stress and antibody response to immunization: a critical review of the human literature. Psychosom Med 2001;63: 7–18.CrossRefGoogle Scholar
Kusnecov, AW, Sved, A, Rabin, BS. Immunological effects of acute versus chronic stress in animals. In: Ader, R, Cohen, N, Felten, DL, eds. Psychoneuroendocrinology, Vol. 2, 3rd Edn. San Diego: Academic Press, 2001: 265–278. Google Scholar
Anisman, H, Lu, ZW, Song, C, Kent, P, McIntyre, DC, Merali, Z. Influence of psychogenic and neurogenic stressors on endocrine and immune activity: differential effects in fast and slow seizing rat strains. Brain Behav Immun 1997;11: 63–74.CrossRefGoogle ScholarPubMed
Lu, ZW, Song, C, Ravindran, AV, Merali, Z, Anisman, H. Influence of a psychogenic and a neurogenic stressor on several indices of immune functioning in different strains of the rat. Brain Beh Immunity 1998;12: 7–22. 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
Matsuda, S, Peng, H, Yoshimura, H, Wen, TC, Fukuda, T, Sakanaka, M. Persistent c-fos expression in the brains of mice with chronic social stress. Neurosci Res 1996;26: 157–170.CrossRefGoogle ScholarPubMed
Melia, KR, Ryabinin, AE, Schroeder, R, Bloom, FE, Wilson, MC. Induction and habituation of immediate early gene expression in rat brain by acute and repeated restraint stress. J Neurosci 1994;14: 5929–5938.Google ScholarPubMed
Watanabe, Y, Stone, E, McEwen, BS. Induction and habituation of c-fos and zif/268 by acute and repeated stressors. Neuroreport 1994;5: 1321–1324.Google ScholarPubMed
Li, HY, Sawchenko, PE. Hypothalamic effector neurons and extended circuitries activated in ‘neurogenic’ stress: a comparison of footshock effects exerted acutely, chronically, and in animals with controlled glucocorticoid levels. J Comp Neurol 1998;393: 244–266.3.0.CO;2-2>CrossRefGoogle ScholarPubMed
Anisman, H, Zacharko, RM. Behavioral and neurochemical consequences associated with stressors. Ann NY Acad Sci 1986;467: 205–225.CrossRefGoogle ScholarPubMed
Kusnecov, AW, Rabin, BS. Stressor-induced alterations of immune function: mechanisms and issues. Int Arch Allergy Immunol 1994;105: 107–121.CrossRefGoogle Scholar
Dhabhar, FS, McEwen, BS. Stress-induced enhancement of antigen-specific cell-mediated immunity. J Immunol 1996;156: 2608–2615.Google ScholarPubMed
Dhabhar, FS, McEwen, BS. Acute stress enhances while chronic stress suppresses cell-mediated immunity in vivo: a potential role for leukocyte trafficking. Brain Behav Immun 1997;11: 286–306.CrossRefGoogle Scholar
Dhabhar, FS, McEwen, BS. Enhancing versus suppressive effects of stress hormones on skin immune function. Proc Natl Acad Sci USA 1999;96: 1059–1064.CrossRefGoogle ScholarPubMed
Dhabhar, FS, Satoskar, AR, Bluethmann, H, David, JR, McEwen, BS. Stress-induced enhancement of skin immune function: a role for gamma interferon. Proc Natl Acad Sci USA 2000;97: 2846–2851.CrossRefGoogle ScholarPubMed
Flint, MS, Miller, DB, Tinkle, SS. Restraint-induced modulation of allergic and irritant contact dermatitis in male and female B6.129 mice. Brain Behav Immunol 2000;14: 256–269. CrossRefGoogle Scholar
Flint, MS, Valosen, JM, Johnson, EA, Miller, DB, Tinkle, SS. Restraint stress applied prior to chemical sensitization modulates the development of allergic contact dermatitis differently than restraint prior to challenge. J Neuroimmunol 2001;113: 72–80.CrossRefGoogle Scholar
Flint, MS, Tinkle, SS. C57BL/6 mice are resistant to acute restraint modulation of cutaneous hypersensitivity. Toxicol Sci 2001;62: 250–256.CrossRefGoogle ScholarPubMed
Blecha, F, Barry, RA, Kelley, KW. Stress-induced alterations in delayed-type hypersensitivity to SRBC and contact sensitivity to DNFB in mice. Proc Soc Exp Biol Med 1982;169: 239–246.CrossRefGoogle ScholarPubMed
Blecha, F, Topliff, D. Lung delayed-type hypersensitivity in stressed mice. Can J Comp Med 1984;48: 211–214.Google ScholarPubMed
Kusnecov, AW, Rabin, BS. Inescapable footshock exposure differentially alters antigen- and mitogen-stimulated spleen cell proliferation in rats. J Neuroimmunol 1993;44: 33–42.CrossRefGoogle ScholarPubMed
Tournier, JN, Mathieu, J, Mailfert, Yet al. Chronic restraint stress induces severe disruption of the T-cell specific response to tetanus toxin vaccine. Immunology 2001;102: 87–93.CrossRefGoogle Scholar
Wood, P G, Karol, MH, Kusnecov, AW, Rabin, BS. Enhancement of antigen-specific humoral and cell-mediated immunity by electric footshock stress in rats. Brain Behav Immun 1993;7: 121–134.CrossRefGoogle ScholarPubMed
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–R1805.Google ScholarPubMed
Sheridan, JF. Norman Cousins Memorial Lecture 1997. Stress-induced modulation of anti-viral immunity. Brain Behav Immun 1998;12: 1–6.CrossRefGoogle Scholar
Jessop, JJ, Bayer, BM. Time-dependent effects of isolation on lymphocyte and adrenocortical activity. J Neuroimmunol 1989;23: 143–147.CrossRefGoogle ScholarPubMed
Shu, J, Stevenson, JR, Zhou, X. Modulation of cellular immune responses by cold water swim stress in the rat. Dev Comp Immunol 1993;17: 357–371.CrossRefGoogle ScholarPubMed
Monjan, AA, Collector, MI. Stress-induced modulation of the immune response. Science 1977;196: 307–308.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
Rinner, I, Schauenstein, K, Mangge, H, Porta, S, Kvetnansky, R. Opposite effects of mild and severe stress on in vitro activation of rat peripheral blood lymphocytes. Brain Behav Immun 1992;6: 130–140.CrossRefGoogle Scholar
Lysle, DT, Lyte, M, Fowler, H, Rabin, BS. Shock-induced modulation of lymphocyte reactivity: suppression, habituation, and recovery. Life Sci 1987;41: 1805–1814.CrossRefGoogle Scholar
Odio, M, Brodish, A, Ricardo, MJ Jr.Effects on immune responses by chronic stress are modulated by aging. Brain Behav Immun 1987;1: 204–215.CrossRefGoogle ScholarPubMed
Bhatnagar, S, Shanks, N, Meaney, MJ. Plaque-forming cell responses and antibody titers following injection of sheep red blood cells in nonstressed, acute, and/or chronically stressed handled and nonhandled animals. Dev Psychobiol 1996;29: 171–181.3.0.CO;2-P>CrossRefGoogle ScholarPubMed
Zalcman, S, Anisman, H. Acute and chronic stressor effects on the antibody response to sheep red blood cells. Pharmacol Biochem Beh 1993;46: 445–452. CrossRefGoogle ScholarPubMed
Shanks, N, Renton, C, Zalcman, S, Anisman, H. Influence of change from grouped to individual housing on a T-cell-dependent immune response in mice: antagonism by diazepam. Pharmacol Biochem Beh 1994;47: 497–502. CrossRefGoogle Scholar
Millan, S, Gonzalez-Quijano, MI, Giordano, M, Soto, L, Martin, AI, Lopez-Calderon, A. Short and long restraint differentially affect humoral and cellular immune functions. Life Sci 1996;59: 1431–1442.CrossRefGoogle Scholar
Fleshner, M, Brennan, FX, Nguyen, K, Watkins, LR, Maier, SF. RU-486 blocks differentially suppressive effect of stress on in vivo anti-KLH immunoglobulin response. Am J Physiol 1996;271: R1344–R1352.Google Scholar
Berkenbosch, F, Wolvers, DA, Derijk, R. Neuroendocrine and immunological mechanisms in stress-induced immunomodulation. J Steroid Biochem Mol Biol 1991;40: 639–647.CrossRefGoogle ScholarPubMed
Persoons, JH, Moes, NM, Broug-Holub, E, Schornagel, K, Tilders, FJ, Kraal, G. Acute and long-term effects of stressors on pulmonary immune functions. Am J Respir Cell Mol Biol 1997;17: 203–208.CrossRefGoogle Scholar
Shanks, N, Kusnecov, AW. Differential immune reactivity to stress in BALB/cByJ and C57BL/6J mice: in vivo dependence on macrophages. Physiol Behav 1998;65: 95–103.CrossRefGoogle Scholar
Lyte, M, Nelson, SG, Thompson, ML. Innate and adaptive immune responses in a social conflict paradigm. Clin Immunol Immunopathol 1990;57: 137–147.CrossRefGoogle Scholar
Zhang, D, Kishihara, K, Wang, B, Mizobe, K, Kubo, C, Nomoto, K. Restraint stress-induced immunosuppression by inhibiting leukocyte migration and Th1 cytokine expression during the intraperitoneal infection of Listeria monocytogenes. J Neuroimmunol 1998;92: 139–151.CrossRefGoogle Scholar
Zwilling, BS, Brown, D, Christner, Ret al. Differential effect of restraint stress on MHC class II expression by murine peritoneal macrophages. Brain Behav Immun 1990;4: 330–338.CrossRefGoogle ScholarPubMed
Mizobe, K, Kishihara, K, Ezz-Din El-Naggar, R, Madkour, GA, Kubo, C, Nomoto, K. Restraint stress-induced elevation of endogenous glucocorticoid suppresses migration of granulocytes and macrophages to an inflammatory locus. J Neuroimmunol 1997;73: 81–89.CrossRefGoogle Scholar
Kizaki, T, Oh-ishi, S, Ohno, H. Acute cold stress induces suppressor macrophages in mice. J Appl Physiol 1996;81: 393–399.Google ScholarPubMed
Ferrandez, MDFM. Effects of age, sex and physical exercise on the phagocytic process of murine peritoneal macrophages. Acta Physiol Scand 1999;166: 47–53.CrossRefGoogle Scholar
Coussons-Read, ME, Maslonek, KA, Fecho, K, Perez, L, Lysle, DT. Evidence for the involvement of macrophage-derived nitric oxide in the modulation of immune status by a conditioned aversive stimulus. J Neuroimmunol 1994;50: 51–58.CrossRefGoogle ScholarPubMed
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
Aviles, H, Monroy, FP. Immunomodulatory effects of cold stress on mice infected intraperitoneally with a 50% lethal dose of Toxoplasma gondii. Neuroimmunomodulation 2001;9: 6–12.CrossRefGoogle ScholarPubMed
Persoons, JH, Schornagel, K, Breve, J, Berkenbosch, F, Kraal, G. Acute stress affects cytokines and nitric oxide production by alveolar macrophages differently. Am J Respir Crit Care Med 1995;152: 619–624.CrossRefGoogle ScholarPubMed
Broug-Holub, E, Persoons, JH, Schornagel, K, Mastbergen, SC, Kraal, G. Effects of stress on alveolar macrophages: a role for the sympathetic nervous system. Am J Respir Cell Mol Biol 1998;19: 842–848.CrossRefGoogle ScholarPubMed
Fleshner, M, Nguyen, KT, Cotter, CS, Watkins, LR, Maier, SF. Acute stressor exposure both suppresses acquired immunity and potentiates innate immunity. Am J Physiol 1998;275: R870–R878.Google ScholarPubMed
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
Kizaki, T, Suzuki, K, Hitomi, Yet al. Activation and apoptosis of murine peritoneal macrophages by acute cold stress. Biochem Biophys Res Commun 2001;283: 700–706.CrossRefGoogle ScholarPubMed
Bonneau, RH, Padgett, DA, Sheridan, JF. Psychoneuroimmune interactions in infectious disease: Studies in animals. In: Ader, R, Felten, DL, Cohen, N, eds. Psychoneuroimmunology, 3rd Edn. San Diego: Academic Press, 2001: 483–498. Google ScholarPubMed
de Groot, J, Van Milligen, FJ, Moonen-Leusen, BW, Thomas, G, Koolhaas, JM. A single social defeat transiently suppresses the anti-viral immune response in mice. J Neuroimmunol 1999;95: 143–151.CrossRefGoogle ScholarPubMed
Plaut, MS, Friedman, SB. Psychosocial factors in infectious disease. In: Ader, R, ed. Psychoneuroimmunology, 1st Edn. Orlando: Academic Press, 1981: 3–30. Google Scholar
Cohen, S, Tyrrell, DA, Smith, AP. Psychological stress and susceptibility to the common cold. N Engl J Med 1991;325: 606–612.CrossRefGoogle ScholarPubMed
Cohen, S, Frank, E, Doyle, WJ, Skoner, DP, Rabin, BS, Gwaltney, JM JrTypes of stressors that increase susceptibility to the common cold in healthy adults. Health Psychol 1998;17: 214–223.CrossRefGoogle ScholarPubMed
Herman, JP, Cullinan, WE. Neurocircuitry of stress: central control of the hypothalamo–pituitary–adrenocortical axis. Trends Neurosci 1997;20: 78–84.CrossRefGoogle ScholarPubMed
Kusnecov, AW, Rossi-George, A. Potentiation of interleukin-1β adjuvant effects on the humoral immune response to antigen in adrenalectomized mice. Neuroimmunomodulation 2001;9: 109–118.CrossRefGoogle Scholar
Besedovsky, HO, Del Rey, A. Immune–neuro-endocrine interactions: facts and hypotheses. Endocr Rev 1996;17: 64–102.CrossRefGoogle ScholarPubMed
Dunn, AJ. Infection as a stressor: a cytokine-mediated activation of the hypothalamo–pituitary–adrenal axis? Ciba Found Symp 1993;172: 226–239; discussion 239–42; 226–239.Google ScholarPubMed
Anisman, H, Zalcman, S, Zacharko, RM. The impact of stressors on immune and central neurotransmitter activity: bidirectional communication. Rev Neurosci 1993;4: 147–180.CrossRefGoogle Scholar