Skip to main content
SpringerLink
Log in
Book cover

Cytokines, Stress, and Depression pp 199–233Cite as

Anhedonic and Anxiogenic Effects of Cytokine Exposure

  • Chapter
  • First Online:

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 461))

Abstract

It is abundantly clear that interactions occur between the immune, endocrine, central, and autonomic nervous systems. Immunologic manipulations (or products of an activated immune system, e.g., cytokines) affect neuroendocrine and central neurotransmitter processes, and conversely, neuroendocrine and central neurotransmitter alterations may impact on immune activity (Anisman, Zalcman, & Zacharko, 1993; Blalock, 1994; Dunn, 1990; Rivier, 1993; Rothwell & Hopkins, 1995). It has been posited that, among other things, the immune system acts like a sensory organ informing the brain of antigenic challenge (Blalock, 1984, 1994). Furthermore, given the nature of the neurochemical changes elicited by antigens and cytokines, it was suggested that immune activation may be interpreted by the CNS as a stressor (Anisman et al., 1993; Dunn, 1990; Dunn, Powell, Meitin, & Small, 1989). To be sure, the effects of systemic Stressors (e.g., those associated with viral insults, bacterial endotoxins, cytokines) are not entirely congruous with those elicited by processive stressors (i.e., those involving higher-order sensory processing, e.g., fear conditioning, exposure to a predator or novel environment) (Herman & Cullinan, 1997). Nevertheless, cytokines may be part of a regulatory loop that, by virtue of effects on CNS functioning, might influence behavioral outputs and may even contribute to the symptoms of behavioral pathologies, including mood and anxiety-related disorders (Anisman et al., 1993; Crnic, 1991). It is curious that while cytokines have found an increasingly greater role in immunotherapy, and may contribute to neurodegenerative processes (Rothwell, Luheshi, & Toulmond, 1996), limited attention has been devoted to behavioral analyses of these cytokines in animal studies.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Alonso, R., Chaudieu, I., Dori, J., Krishnamurthy, A., Quirion, R., & Boksa, P. (1993). Interleukin-2 modulates evoked release of [3H]dopamine in rat cultured mesencephalic cells, Journal of Neurochemistry, 61, 1284–1290.

    Article  CAS  PubMed  Google Scholar 

  • Anisman, H., Zalcman, S., Shanks, N., & Zacharko, R. M. (1991). Multisystem regulation of performance deficits induced by Stressors: An animal model of depression. In A. Boulton, G. Baker, & M. Martin-Iverson (Eds.), Neuromethods, vol. 19: Animal Models of Psychiatry, II. (pp. 1–59). New Jersey: Humana Press.

    Google Scholar 

  • Anisman, H., Zalcman, S., & Zacharko, R. M. (1993). The impact of Stressors on immune and central neurotransmitter activity: Bidirectional communication. Reviews in the Neurosciences, 4, 147–180.

    Article  CAS  PubMed  Google Scholar 

  • Anisman, H., Kokkinidis, L., & Merali, Z. (1996). Influence of interleukin-2 on responding for electrical brain stimulation from the hypothalamus. Brain Research, 731, 1–11.

    Article  CAS  PubMed  Google Scholar 

  • Anisman, H., Lu, Z. W., Song, C, Kent, P., Mclntyre, D. C, & Merali, Z. (1997). Influence of psychogenic and neurogenic Stressors on endocrine and immune activity: differential effects in fast and slow seizing rat strains. Brain, Behavior, and Immunity, 11, 63–74.

    Article  CAS  PubMed  Google Scholar 

  • Anisman, H., Kokkinidis, L., Borowski, T., & Merali, Z. (1998a). Differential effects of interleukin (IL)-l, IL-2, and IL-6 on responding for rewarding lateral hypothalamic stimulation. Brain Research, 779, 177–187.

    Article  CAS  PubMed  Google Scholar 

  • Anisman, H., Ravindran, A. V., Griffiths, J., & Merali, Z. (1998b). Behavioral, endocrine, and cytokine correlates of major depression and dysthymia with typical or atypical features. Molecular Psychiatry, in press

    Google Scholar 

  • Araujo, B. M., Lapchak, P. A., Collier, B., & Quirion, R. (1989). Localization of interleukin-2 immunoreactivity and interleukin-2 receptors in the rat brain: interaction with the cholinergic system. Brain Research, 498, 257–266.

    Article  CAS  PubMed  Google Scholar 

  • Ban, E. M., Haour, F., & Lenstra, R. (1992). Brain interleukin-1 gene expression induced by peripheral lipopolysaccharide administration. Cytokine, 4, 48–54.

    Article  CAS  PubMed  Google Scholar 

  • Banks, W. A., Ortz, L., Plotkin, S. R., & Kasten, A. J. (1991). Human interleukin (IL)-l alpha, murine IL-1 alpha, and murine IL-2 beta are transported from blood to brain in the mouse by a shared saturable mechanism. Journal of Pharmacological and Experimental Therapeutics, 259, 988–996.

    CAS  Google Scholar 

  • Bartanusz, V, Jezova, D., Bertini, L. T., Tilders, F. J., Aubry, J. M., & Kiss, J. Z. (1993). Stress-induced increase in vasopressin and corticotropin-releasing factor expression in hypophysiotrophic paraventricular neurons. Endocrinology, 132, 895–902.

    Article  CAS  PubMed  Google Scholar 

  • Bartholemew, S. A. & Hoffman, S. A. (1993). Effects of peripheral cytokine injections on multiple unit activity in the anterior hypothalamic area of the mouse. Brain, Behavior, and Immunity, 7, 301–316.

    Article  Google Scholar 

  • Blalock, J. E. (1984). The immune system as a sensory organ. Journal of Immunology, 132, 1067–1070.

    CAS  Google Scholar 

  • Blalock, J. E. (1994). The syntax of immune-neuroendocrine communication. Immunology Today, 15, 504–511.

    Article  CAS  PubMed  Google Scholar 

  • Bluthe, R. M., Dantzer, R., & Kelley, K. W. (1989). Corticotropin releasing hormone is not involved in the behavioral effects of peripherally injected interleukin-1 in the rat. Neuroscience Research Communincations, 5, 149–154.

    CAS  Google Scholar 

  • Bluthe, R. M., Michaud, B., Kelley, K. W., & Dantzer, R. (1996). Vagotomy attenuates behavioral effects of interleukin-1 injected peripherally but not centrally. Neuroreport, 7, 1485–1488.

    Article  CAS  PubMed  Google Scholar 

  • Bluthe, R. M., Dantzer, R., & Kelley, K. W. (1997). Central mediation of the effects of interleukin-1 on social exploration and body weight in mice. Psychoneuroendocrinology, 22, 1–11.

    Article  CAS  PubMed  Google Scholar 

  • Borowski, T, Kokkinidis, L., Merali, Z., & Anisman, H. (1997). Behavioral and central monoamine alterations induced by interleukin-1, interleukin-6, and lipopolysaccharide. Society for Neurosciences Abstract, 23, 1508.

    Google Scholar 

  • Brady, L. S., Lynn, A. B., Herkenham, M., & Gottesfeld, Z. (1994). Systemic interleukin-1 induces early and late patterns of c-fos mRNA expression in brain. Journal of Neuroscience, 14, 4951–4964.

    Article  CAS  PubMed  Google Scholar 

  • Brebner, K., Hayley, S., Lacosta, S., Zacharko, R., Merali, Z., & Anisman, H. (1998). Synergistic actions of interleukin (IL)-lβ, IL-6, and TNFα: Central neurochemical, neuroendocrine and behavioral alterations. Society for Neurosciences Abstract, in press.

    Google Scholar 

  • Bret-Dibat, J. L., Bluthe, R. M., Kent, S., Kelley, K. W., & Dantzer, R. (1995). Lipopolysaccharide and interleukin-1 depress food-motivated behavior in mice by a vagal-mediated mechanism. Brain, Behavior, and Immunity, 9, 242–246.

    Article  CAS  PubMed  Google Scholar 

  • Buttini, M. & Boddeke, H. (1995). Peripheral lipopolysaccharide stimulation induces interleukin-Iβ messenger RNA in rat brain microglial cells. Neuroscience, 65, 523–530.

    Article  CAS  PubMed  Google Scholar 

  • Capuron, L., Ravaud, A., Radat, F., Dantzer, R., & Goodall, G. (1998). Effects of interleukin-2 and alpha interferon cytokine immunotherapy on the mood and cognitive performance of cancer patients. Neuroimmunomodulation, 5, 9.

    Article  Google Scholar 

  • Caraceni, A., Martini, G, Belli, F., Mascheroni, L., Rivoltini, L., Arienti, F., & Cascinelli, N. (1992). Neuropsychological and neurophysiological assessment of the central effects of interleukin-2 administration, European Journal of Cancer, 29A, 1266–1269.

    Google Scholar 

  • Connor, T. J. & Leonard, B. E. (1998). Depression, stress and immunological activation: The role of cytokines in depressive disorders. Life Sciences, 62, 583–606.

    Article  CAS  PubMed  Google Scholar 

  • Connor, T., Song, G, Leonard, B. E., Merali, Z., & Anisman, H. (1998). An assessment of the effects of central interleukin-1 β,-2,-6 and tumor necrosis factor-α administration on some behavioural, neurochemical, endocrine, and immune parameters in the rat. Neuroscience, 84, 923–933.

    Article  CAS  PubMed  Google Scholar 

  • Crnic, L. S. (1991). Behavioral consequences of viral infection. In R. Ader, D. L. Feiten, & N. Cohen (Eds.), Psychoneuroimmunology (pp. 749–770). San Diego: Academic Press.

    Chapter  Google Scholar 

  • Dantzer, R., Bluthe, R. M., Aubert, A., Goodall, G, Bret-Dibat, J-L., Kent, S., Goujon, E., Laye, S., Parnet, P., & Kelley, K. W. (1996). Cytokine actions on behavior. In N. J. Rothwell (Ed.), Cytokines and the Nervous System, (pp. 117–144). London: Landes.

    Chapter  Google Scholar 

  • Day, H. E. & Akil, H. (1996). Differential pattern of c-fos mRNA in the rat brain following central and systemic administration of interleukin-1-beta: implications for mechanism of action. Neuroendocrinology, 63, 207–218.

    Article  CAS  PubMed  Google Scholar 

  • Denicoff, K. D., Rubinow, D. R., Papa, M. Z., Simpson, L., Seipp, L. A., Lotze, M. T., Chang, A. E., Rosenstein, D., & Rosenberg, S. A. (1987). The neuropsychiatric effects of treatment with interleukin-2 and lymphokine-activated killer cells. Annals of Internal Medicine, 107, 293–300.

    Article  CAS  PubMed  Google Scholar 

  • De Sarro, G., Gareri, P., Sinopoli, V. A., David, E., & Rotiroti, D. (1997). Comparative, behavioural, and electrocortical effects of tunor necrosis factor-alpha and interleukin-1 microinjected into the locus coeruleus of rat. Life Sciences, 60, 555–564.

    Article  PubMed  Google Scholar 

  • De Simoni, M. G, Del Bo, R., De Luigi, A., Simard, S., & Forloni, G. (1995). Central endotoxin induces different patterns of interleukin (IL)-lb and IL-6 messenger robonucleic acid expression and IL-6 secretion in the brain and periphery. Endocrinology, 136, 897–902.

    Article  PubMed  Google Scholar 

  • Dunn, A., J. (1990). Interleukin-1 as a stimulator of hormone secretion. Progress in NeuroEndocrinlmmunology, 3, 26–34.

    Google Scholar 

  • Dunn, A. J. (1995). Interactions between the nervous system and the immune system. In F. E. Bloom & D. J. Kupfer (Eds.), Psychopharmacology: The Fourth Generation of Progress (pp. 719–731). New York: Raven Press.

    Google Scholar 

  • Dunn, A. J. & Welch, J. (1991). Stress-and endotoxin-induced increases in brain tryptophan and serotonin metabolism depend on sympathetic nervous system activity. Journal of Neurochemistry, 57, 1615–1622.

    Article  CAS  PubMed  Google Scholar 

  • Dunn, A. J., Powell, M. L., Meitin, C, & Small, P. A. (1989). Virus infection as a stressor: Influenza virus elevates plasma concentrations of corticosterone, and brain concentrations of MHPG and tryptophan. Physiology and Behavior, 45, 591–594.

    Article  CAS  PubMed  Google Scholar 

  • Elmquist, J. K., Scammell, T. E., & Saper, C. B. (1997). Mechanisms of CNS response to systemic immune challenge: the febrile response. Trends in Neurosciences, 20, 565–570.

    Article  CAS  PubMed  Google Scholar 

  • Ericsson, A., Kovacs, K. J., & Sawchenko, P. E. (1994). A functional anatomical analysis of central pathways subserving the effects of interleukin-1 on stress-related neuroendocrine neurons. Journal of Neuroscience, 14, 89–913.

    Article  Google Scholar 

  • Ericcson, A., Ek, M., Wahlstrom, I., Kovacs, K., Liu, C-L., Hart, R., & Sawchenko, P. E. (1996). Pathways and mechanisms for interleukin-1 mediated regulation of the hypothalamo-pituitary-adrenal axis. In R. McCarty, G. Aguilera, E. L. Sabban, & R. Kvetnancky (Eds.), Stress: molecular genetic and neurobiological advances (pp. 101–120). New York: Gordon & Breach.

    Google Scholar 

  • Ericsson, A., Arias, C, & Sawchenko, P. E. (1997). Evidence for an intermedullary prostaglandin-dependent mechanism in the activation of stres-related neuroendocrine circuitry by intravenous interleukin-1. Journal of Neuroscience, 17, 7166–7179.

    Article  CAS  PubMed  Google Scholar 

  • Fibiger, H. C. & Phillips, A. G. (1988). Mesocorticolimbic dopamine systems and reward. In P. Kalivas & C. Nemeroff (Eds.), The Mesocorticolimbic System, (pp. 206–215). New York: New York Academy of Science.

    Google Scholar 

  • Gabellec, M-M., Griffais, R., Fillion, G, & Haour, F. (1996). Interleukin-1 receptors type I and type II in the mouse brain: kinetics of mRNA expressions after peripheral administration of bacterial lipopolysaccharide. Journal of Neuroimmunology, 66, 65–70.

    Article  CAS  PubMed  Google Scholar 

  • Gaillard, R. C. (1995). Immunoendocrine interactions at the hypothalamo-pituitary level. Annales D’Endocrinologie, 56, 561–566.

    CAS  PubMed  Google Scholar 

  • Gold, P. W., Chrousos, G. P., Kellner, C, Post, R. M., Roy, A., Augerinas, P., Schulte, H., Oldgield, E. H., & Loriaux, D. L. (1984). Psychiatric implications of basic and clinical studies with corticotropin-releasing factor. American Joural of Psychiatry 141 619–627

    Article  CAS  Google Scholar 

  • Gray, T. S. (1991). Amygdala: Role in autonomic, and neuroendocrine responses to stress. In J. A. McCubbin, P. G. Kaufmann, & C. B. Nemeroff (Eds.), Stress, Neuropeptides, and Systemic Disease (pp. 37–53). New York: Academic Press.

    Chapter  Google Scholar 

  • Griffiths, J., Ravindran, A. V., Merali, Z., & Anisman, H. (1996). Immune and behavioral correlates of typical and atypical depression. Society for Neuroscieces Abstract, 22, 1350.

    Google Scholar 

  • Gutierrez, E. G., Banks, W. A., & Kastin, A. J. (1993). Murine tumor necrosis factor alpha is transported from blood to brain in the mouse. Journal of Neuroimmunology, 47, 169–176.

    Article  CAS  PubMed  Google Scholar 

  • Hanisch, U-W. & Quirion, R. (1996). Interleukin-2 as a neuroregulatory cytokine. Brain Research Reviews, 21, 246–284.

    Article  Google Scholar 

  • Hanisch, U-W, Seto, D., & Quirion, R. (1993). Modulation of hippocampal acetylcholine release: a potent central action of interleukin-2. Journal of Neuroscience, 13, 3368–3374.

    Article  CAS  PubMed  Google Scholar 

  • Hanisch, U-W, Rowe, W., Sharma, S., Meaney, M. J., & Quirion, R. (1994). Hypothalamic-pituitary-adrenal activity during chronic central administration of interleukin-2. Endocrinology, 135, 2465–2472.

    Article  CAS  PubMed  Google Scholar 

  • Hanisch, U-W, Neuhaus, J., Rowe, W, van Rossum, D., Moller, T., Kettenmann, H., & Quirion, R. (1997). Neurotoxic consequences of central long-term administration of interleukin-2 in rats. Neuroscience, 79, 799–818.

    Article  CAS  PubMed  Google Scholar 

  • Haour, F., Marquette, G, Ban, E., Crumeyrolle-Arias, M., Rostene, W., Tsiang, H. & Fillion, G. (1995). Receptors for interleukin-1 in the central nervous system and neuroendocrine systems. Annales d’Endocrinologie, 56, 173–179.

    CAS  PubMed  Google Scholar 

  • Harbuz, M. S. & Lightman, S. L. (1992). Stress and the HPA axis: Acute, chronic and immunological activation. Journal of Endocrinology, 134, 327–339.

    Article  CAS  Google Scholar 

  • Hayley, S. Brebner, K., Staines, W, Merali, Z., & Anisman, H. (1998). Sensitization effects of tumor necrosis factor-a: behavioral, neuroendocrine and neurochemical alterations. Society for Neurosciences Abstract, in press.

    Google Scholar 

  • Hebb, A. L. O., Zacharko, R. M., & Anisman, H. (1998). Self-stimulation from the mesencephalon following intraventricular interleukin-2 administration. Brain Research Bulletin, 45, 549–556.

    Article  CAS  PubMed  Google Scholar 

  • Heilig, M., Koob, G. F., Ekman, R., & Britton, K. T. (1994). Corticotropin releasing factor and neuropeptide Y: role in emotional integration. Trends in Neurosciences, 17, 80–84.

    Article  CAS  PubMed  Google Scholar 

  • Hellerstein, M. K., Meydani, S. R, Meydani, M., Wu, K., & Dinarello, G A. (1989). Interleukin-1-induced anorexia in the rat. Influence of prostaglandins. Journal of Clinical Investigation, 84, 228–235.

    Article  CAS  PubMed Central  Google Scholar 

  • Herman, J. P. & Cullinan, W. E. (1997). Neurocircuitry of stress: Central control of hypothalamo-pituitary-adrenocortical axis. Trends in Neurosciences, 20, 78–84.

    Article  CAS  PubMed  Google Scholar 

  • Holden, R. J. & Pakula, I. S. (1996). The role of tumor necrosis factor-alpha in the pathogenesis of anorexia and bulimia nervosa, cancer cachexia and obesity. Medical Hypotheses, 47, 423–438.

    Article  CAS  PubMed  Google Scholar 

  • Holsboer, F. (1995). Neuroendocrinology of Mood Disorders. In F. E. Bloom & Kupfer, D. J. (Eds.), Psychopharmacology: The Fourth Generation of Progress (pp. 957–969). New York: Raven Press.

    Google Scholar 

  • Hopkins, S. J., Rothwell, N. J. (1995). Cytokines and the nervous system. Trends in Neurosciences, 18, 83–88.

    Article  CAS  PubMed  Google Scholar 

  • Ilyin, S. E. & Plata-Salaman, C. R. (1996). In vivo regulation of the IL-1 beta system (ligand, receptors I and II, receptor accessory protein, and receptor antagonist) and TNF-alpha mRNAs in specific brain regions. Biochemical and Biophysical Research Communications, 227, 861–867.

    Article  CAS  PubMed  Google Scholar 

  • Imura, H., Fukata, J-I., & Mori, T. (1991). Cytokines and endocrine function: an interaction between the immune and neuroendocrine systems. Clinical Endocrinology, 35, 107–115.

    Article  CAS  PubMed  Google Scholar 

  • Kalivas, P. W. & Duffy, P. (1995). Selective activation of dopamine transmission in the shell of the nucleus accumbens by stress. Brain Research, 675, 325–328.

    Article  CAS  PubMed  Google Scholar 

  • Katsumata, S. & Satoh, M. (1993). In situ hybridization study of interleukin-1β mRNA induced by kainic acid in the rat brain. Molecular Brain Research, 20, 153–161.

    Article  PubMed  Google Scholar 

  • Kent, S., Bluthe, R-M., Kelley, K. W, & Dantzer, R. (1992). Sickness behavior as a new target for drug development. Trends in Pharmacological Sciences, 13, 24–28.

    Article  CAS  PubMed  Google Scholar 

  • Kent, S., Rodriguez, F., Kelley, K. W., & Dantzer, R. (1994). Reduction in food and water intake induced by microinjection of interleukin-1 beta in the ventromedial hypothalamus of the rat. Physiology and Behavior, 56, 1031–1036.

    Article  CAS  PubMed  Google Scholar 

  • Kent, S., Bret-Dibat, J. L., Kelley, K. W, & Dantzer, R. (1996). Mechanisms of sickness-induced decreases in food-motivated behavior. Neuroscience and Biobehavioral Reviews, 20, 171–175.

    Article  CAS  PubMed  Google Scholar 

  • Kinouchi, K., Brown, G., Pasternak, G., & Donner, D. B. (1991). Identification and characterization of receptors for tumor necrosis factor-a in the brain. Biochemical and Biophysical Research Communications, 181, 1532–1538.

    Article  CAS  PubMed  Google Scholar 

  • Kluger, M. J. (1991). Fever: Role of endogenous pyrogens and cryogens. Physiologal Reviews, 71, 93–127.

    Article  CAS  Google Scholar 

  • Kokkinidis, L. & Anisman, H. (1980). Amphetamine models of paranoid schizophrenia: An overview and elaboration of animal environmentation Psychological Bulletin 88 551–579

    Article  CAS  PubMed  Google Scholar 

  • Lacosta, S., Kulczycki, J., Merali, Z., Anisman, H. (1996). Behavioral, endocrine and central neurochemical alterations induced by interleukin-1. Society for Neurosciences Abstract, 22, 2059.

    Google Scholar 

  • Lacosta, S., Merali, Z., & Anisman, H. (1998a). Behavioral and neurochemical consequences of acute and chronic interleukin-2 administration. Society for Neurosciences Abstract, in press, (a)

    Google Scholar 

  • Lacosta, S., Merali, Z., & Anisman, H. (1998b). Influence of interleukin-1 on exploratory behaviors, plasma ACTH and cortisol, and central biogenic amines in mice. Psychopharmacology, in press, (b)

    Google Scholar 

  • Lapchak, P. A. (1992). A role for interleukin-2 in the regulation of striatal dopaminergic function. Neuroreport, 3, 165–168.

    Article  CAS  PubMed  Google Scholar 

  • Laye, S., Bluthe, R. M., Kent, S., Combe, C, Medina, C, Parnet, P., Kelly, K., & Dantzer, R. (1995). Subdiaphragmatic vagotomy blocks induction of IL-1 beta mRNA in mice brain in response to peripheral LPS. American Journal of Physiology, 37, R1327–R1331.

    Google Scholar 

  • Lee, Y. & Davis, M. (1997). Role of the hippocampus, bed nucleus of the stria terminalis, and the amygdala in the excitatory effect of corticotropin-releasing hormone on the acoustic startle reflex. Journal of Neuroscience, 17, 6434–7446.

    Article  CAS  PubMed  Google Scholar 

  • Linthorst, A. C. E., Flachskamm, C, Muller-Preuss, P. Holsboer, F., & Reul, J. M. H. M. (1995). Effect of bacterial endotoxin and interleukin-1 b on hippocampal serotonergic neurotransmision, behavioral activity, and free corticosterone levels: An in vivo microdialysis study. Journal of Neuroscience, 15, 2920–2934.

    Article  CAS  PubMed  Google Scholar 

  • Liu, L., Kita, T., Tanaka, N., & Kinoshita, Y. (1996). The expression of tumor necrosis factor in the hypothalamus after treatment with lipopolysaccharide. International Journal of Experimental Pathology, 77, 37–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Loddick, S. A., MacKenzie, A., & Rothwell, N. J. (1996). An ICE inhibitor, z-VAD-DCB attenuates ischaemic brain daage in the rat. Neuroreport, 7, 1465–1468.

    Article  CAS  PubMed  Google Scholar 

  • Loddick, S. A., Wong, M. L., Bongiorno, P. B., Gold, P. W., Licinio, J., & Rothwell, N. J. (1997). Endogenous interleukin-1 receptor antagonist is neuroprotective. Biochemical and Biophysical Research Communications, 234, 211–215.

    Article  CAS  PubMed  Google Scholar 

  • Maes, M. (1995). Evidence for an immune response in major depression: A review and hypothesis. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 19, 11–38.

    Article  CAS  PubMed  Google Scholar 

  • Maes, M., Bosmans, E., Suy, E., Vandervorst, C, DeJonckheere, C, Minner, B., & Raus, J. (1991). Depression-related disturbances in mitogen-induced lymphocyte responses, interleukin-1β, and soluble interleukin-2-receptor production. Acta Psychiatrica Scandinavica, 84, 379–386.

    Article  CAS  PubMed  Google Scholar 

  • Maes, M., Lambrechts, J., Bosmans, E., Jacobs, J., Suy, E., Vandervorst, C, DeJonckheer, C, Minner, B., & Raus, J. (1992). Evidence for a systemic immune activation during depression: Results of leukocyte enumeration by flow cytometry in conjunction with monoclonal antibody staining. Psychological Medicine, 22, 45–53.

    Article  CAS  PubMed  Google Scholar 

  • Maes, M., Stevens, W. J., Peeters, D., DeClerck, L. S., Bridts, C. H., Peeters, D., Schotte, G, & Cosyns, P. (1993). Significantly increased expression of T-cell activation markers (interleukin-2 and HLA-DR) in depression: further evidence for an inflammatory process during that illness. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 17, 241–255.

    Article  CAS  PubMed  Google Scholar 

  • Maes, M., Meltzer, H. Y, Bosmans, E., Bergmans, R., Vandoolaeghe, E., Ranjan, R., & Desnyder, R. (1995). Increased plasma concentrations of interleukin-6, soluble interleukin-6, soluble interleukin-2, and transferrin receptor in major depression. Journal of Affective Disorders, 34, 301–309.

    Article  CAS  PubMed  Google Scholar 

  • Maier, S. F. & Watkins, L. R. (1995). Intracerebroventricular interleukin-1 receptor antagonist blocks the enhancement of fear conditioning and interference with escape produced by inescapable shock. Brain Research, 695, 279–286.

    Article  CAS  PubMed  Google Scholar 

  • Maier, S. F. & Watkins, L. R. (1998). Cytokines for psychologists: Implications of bidirectional immune-to-brain communication for understanding behavior, mood, and cognition. Psychological Review, 105, 83–107.

    Article  CAS  PubMed  Google Scholar 

  • Masana, M. I., Heyes, M. P., & Mefford, I. N. (1990). Indomethacin prevents increased catecholamine turnover in rat brain following systemic endotoxin challenge. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 74, 609–621.

    Article  Google Scholar 

  • Mclntyre, D. C. (1980). Amygdala kindling in rats: facilitation after local amygdala norepinephrine depletion with 6-hydroxydopamine. Experimental Neurology, 69, 395–407.

    Article  Google Scholar 

  • Mefford, I. N. & Heyes, M. P. (1990). Increased biogenic amine release in mouse hypothalamus following immunological challenge: antagonism by indomethacin. Journal of Neuroimmunology, 27, 55–61.

    Article  CAS  PubMed  Google Scholar 

  • Mefford, I. N., Masters, C. F., Heyes, M. P., & Eskay, R. L. (1991). Cytokine-induced activation of the neuroendocrine stress axis persists in endotoxin-tolerant mice. Brain Research, 557, 327–330.

    Article  CAS  PubMed  Google Scholar 

  • Merali, Z., Lacosta, S., & Anisman, H. (1997). Effects of interleukin-lβ and mild stress on alterations of central monoamines: A regional microdialysis study. Brain Research, 761, 225–235.

    Article  CAS  PubMed  Google Scholar 

  • Meyers, C. A. & Valentine, A. D. (1995). Neurological and psychiatric adverse effects of immunological therapy, CNS Drugs, 3, 56–68.

    Article  Google Scholar 

  • Minami, M., Kuraishi, Y., Yamaguchi, T., Nakai, S., Hirai, Y., & Satoh, M. (1990). Convulsants induce inter-leukin-lb messenger RNA in rat brain. Biochemical and Biophysical Research Communications, 171, 832–837.

    Article  CAS  PubMed  Google Scholar 

  • Minami, M., Kuraishi, Y., Yamaguchi, T., Nakai, S., Hirai, Y, & Satoh, M. (1991). Immobilization stress induces interleukin-lβ mRNA in rat hypothalamus. Neuroscience Letters, 123, 254–256.

    Article  CAS  PubMed  Google Scholar 

  • Mohankumar, P. S. & Quadri, S. K. (1993). Systemic administration of interleukin-1 stimulates norepinephrine release in the paraventricular nucleus. Life Sciences, 52, 1961–1967.

    Article  CAS  PubMed  Google Scholar 

  • Mohankumar, P. S., Thyagarajan, S., & Quadri, S. K. (1991). Interleukin-1 stimulates the release of dopamine and dihydroxyphenylacetic acid from hypothalamus in vivo. Life Sciences, 48, 925–930.

    Article  CAS  PubMed  Google Scholar 

  • Mohankumar, P. S., Thyagarajan, S., & Quadri, S. K. (1993). Interleukin-lβ increases 5-hydroxyindoleacetic acid release in the hypothalamus in vivo. Brain Research Bulletin, 31, 745–748.

    Article  CAS  PubMed  Google Scholar 

  • Mohapel, P. & Mclntyre, D. C. (1998). Amygdala kindling-resistant (SLOW) or-prone (FAST) rat strains show differential fear responses. Behavioral Neurosciences, in press.

    Google Scholar 

  • Moldofsky, H. (1995). Sleep and the immune system. International Journal of Immunopharmacology, 17, 649–665.

    Article  CAS  PubMed  Google Scholar 

  • Muaramami, N., Fukata, J., Tsukada, T., Kobayashi, H., Ebisui O. Segawa, H., Muro, S., Imura, H., & Nakao, K. (1993). Bacterial lipopolysaccharide expression of interleukin-6 messenger ribonucleic acid in the rat hypothalamus, pituitary, adrenal gland, and spleen. Endocrinology, 133, 2574–2578.

    Article  Google Scholar 

  • Mullar, N. & Ackenheil, M. (1998). Psychoneuroimmunology and the cytokine action in the CNS: Implications for psychiatric disorders. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 22, 1–33.

    Article  Google Scholar 

  • Nassberger, L. & Traskman-Bendz, L. (1993). Increased soluble interleukin-2 receptor concentrations in suicide attempters. Acta Psychiatrica Scandinavica, 88, 48–52.

    Article  CAS  PubMed  Google Scholar 

  • Nemeroff, C. B. (1996). The coricotropin-releasing factor (CRF) hypothsesis of depression: New findings and new directions. Molecular Psychiatry, 1, 336–342.

    CAS  PubMed  Google Scholar 

  • Nguyen, K. T., Deak, T, Owens, S. M., Kohno, T, Fleshner, M., Watkins, L. R., & Maier, S. F. (1998). Exposure to acute stress induces brain interleukin-lβ protein in the rat. Journal Neuroscience, 18, 2239–2246.

    Article  CAS  PubMed  Google Scholar 

  • Petitto, J. M., McCarthy, D. B., Rinker, C. M., Huang, Z., & Getty, T. (1997). Modulation of behavioral and neurochemical measures of forebrain dopamine function in mice by species-specific interleukin-2. Journal of Neuroimmunology, 73, 183–190.

    Article  CAS  PubMed  Google Scholar 

  • Pitossi, F., del Rey, A., Kabiersch, A., & Besedovsky, H. (1997). Induction of cytokine transcripts in the CNS and pituitary following peripheral administration of endotoxin to mice. Journal of Neuroscience Research, 48, 287–298.

    Article  CAS  PubMed  Google Scholar 

  • Plata-Salaman, C. R. (1989). Immunomodulators and feeding regulation: A humoral link between the immune and nervous systems. Brain, Behavior and Immunity, 3, 193–213.

    Article  CAS  Google Scholar 

  • Plata-Salaman, C. R. (1994). Meal patterns in response to the intracerebroventricular administration of interleukin-1<b> in rats. Physiology and Behavior, 55, 727–733.

    Article  CAS  PubMed  Google Scholar 

  • Plata-Salaman, C. R. (1998). Cytokines and anorexia: A brief overview. Seminars in Oncology, 25, 64–72.

    CAS  PubMed  Google Scholar 

  • Quan, N., Sundar, S. K., & Weiss, J. M. (1994). Induction of interleukin-1 in various brain regions after peripheral and central injections of lipopolysaccharide. Journal of Neuroimmunology, 49, 125–134.

    Article  CAS  PubMed  Google Scholar 

  • Raber, J., Koob, G. F., & Bloom, F. E. (1995). Interleukin-2 (IL-2) induces corticotropin-releasing factor (CRF) release from the amygdala and involves a nitric oxide-mediated signaling: Comparison with the hypothalamic response. Journal of Pharmacology and Experimental Therapeutics, 272, 815–824.

    CAS  Google Scholar 

  • Rajora, N., Boccoli, G., Burns, D., Sharma, S., Catania, A. P., & Lipton, J. M. (1997). α-MSH modulates local and circulating tumor necrosis factor-α in experimental brain inflammation. Journal of Neuroscience, 15, 2181–2186.

    Article  Google Scholar 

  • Richardson, N. R. & Roberts, D. C. S. (1996). Progressive ratio schedules in drug self-administration studies in rats: a method to evaluyate reinforcing efficacy. Journal of Neuroscience Methods, 66, 1–11.

    Article  CAS  PubMed  Google Scholar 

  • Rivest, S. (1995). Molecular mechanisms and neural pathways mediating the influence of interleukin-1 on the activity of neuroendocrine CRF motoneurons in the rat. International Journal of Developmental Neuroscience, 13, 135–146.

    Article  CAS  PubMed  Google Scholar 

  • Rivest, S. & Rivier, C. (1994). Stress and interleukin-1 beta-induced activation of c-Fos, Ngfi-B, and CRF gene expression in the hypothalamic PVN—Comparison between Sprague-Dawley, Fisher-344, and Lewis rats. Journal of Neuroendocrinology, 6, 101–117.

    Article  CAS  PubMed  Google Scholar 

  • Rivest, S. & Laflamme, N. (1995). Neuronal activity and neuropeptide gene transcription in the brains of immune-challenged rats. Journal of Neuroendocrinology, 7, 501–525.

    Article  CAS  PubMed  Google Scholar 

  • Rivier, C. (1993). Effect of peripheral and central cytokines on the hypothalamic-pituitary-adrenal axis of the rat. Annals of the New York Academy of Sciences, 697, 97–105.

    Article  CAS  PubMed  Google Scholar 

  • Rothwell, N. J. & Hopkins, S. J. (1995). Cytokines and the nervous system II: Actions and mechanisms of action. Trends in Neurosciences, 18, 130–136.

    Article  CAS  PubMed  Google Scholar 

  • Rothwell, N. J., Luheshi, G., & Toulmond, S. (1996). Cytokines and their receptors in the central nervous system: physiology, pharmacology, and pathology. Pharmacology and Therapeutics, 69, 85–95.

    Article  CAS  PubMed  Google Scholar 

  • Rothwell, N. J., Loddick, S. A., & Stroemer, P. (1997). Interleukins and cerbral ischemia. International Review of Neurobiology, 40, 291–298.

    Google Scholar 

  • Sato, S., Reiner, S. L., Jensen, M. A., & Roos, R. P. (1997). Central nervous system mRNA expression following Theiler’s murine encephalomyelitis virus infection. Journal of Neuroimmunology, 76, 213–223.

    Article  CAS  PubMed  Google Scholar 

  • Sawchenko, P. E., Brown, E. R., Chan, R. K. W., Ericsson, A., Li, H.-Y, Roland, B. L., & Kovacs, K. J. (1996). The paraventricular nucleus of the hypothalamus and the functional neuroanatomy of visceromotor responses to stress. Progress in Brain Research, 107, 201–222.

    Article  CAS  PubMed  Google Scholar 

  • Schmidt, E. D., Janszen, A. W. J. W., Wouterlood, F. G., & Tilders, F. J. H. (1995). Interleukin-1 induced long-lasting changes in hypothalamic corticotropin-releasing hormone (CRH) neurons and hyperrespon-siveness of the hypothalamic-pituitary-adrenal axis. Journal of Neuroscience, 15, 7417–7426.

    Article  CAS  PubMed  Google Scholar 

  • Schobitz, B., De Kloet, E. R., Sutanto, W., & Holsboer, F. (1993). Cellular localization of interleukin-6 mRNA and interleukin 6 mRNA in rat brain. European Journal of Neuroscience, 5, 1426–1435.

    Article  CAS  Google Scholar 

  • Seto, D., Karr, S., & Quirion, R. (1997). Evidence for direct and indirect mechanisms in the potent modulatory action of interleukin-2 on the release of acetylcholine in rat hippocampal slices. British Journal of Pharmacology, 120, 1151–1157.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shintani, F., Kanba, S., Nakaki, T., Nibuya, M., Kinoshita, N., Suzuki, E., Yagi, G., Kato, R., & Asai M. (1993). Interleukin-1β augments release of norepinephrine, dopamine and serotonin in the rat anterior hypothalamus, Journal of Neuroscience, 13, 3574–3581.

    Article  CAS  PubMed  Google Scholar 

  • Shintani, F., Nakaki, T., Kanba, S., Sato, K., Kato, R., & Asai, M. (1995a). Role of interleukin-1 in stress responses. Molecular Neurobiology, 10, 41–71. a

    Article  Google Scholar 

  • Shintani, F., Nakaki, T., Kanba, S., Sato, K., Yagi, G., Shiozawa, M., Aiso, S., Kato, R., & Asai, M. (1995b). Involvement of interleukin-1 in immibilization stress-induced increase in plasma adrenocorticotropic hormone and in release of hypothalamic monoamines in the rat. Journal of Neuroscience, 15, 1961–1970. b

    Article  CAS  PubMed  Google Scholar 

  • Sluzewska, A., Rybakowski, J. K., Laciak, M., Mackiewicz, A., Sobieska, M., & Wiktorowicz, K. (1995). Inter-leukin-6 serum levels in depressed patients before and after treatment with fluoxetine. Annals of the New York Academy of Sciences, 762, 474–476.

    Article  CAS  PubMed  Google Scholar 

  • Smagin, G. N., Swiergiel, A. H., & Dunn, A. J. (1996). Peripheral administration of interleukin-1 increases extracellular concentrations of norepinephrine in rat hypothalamus: Comparison with plasma corticosterone. Psychoneuroendocrinology, 21, 83–93.

    Article  CAS  PubMed  Google Scholar 

  • Smith, R. S. (1991). The macrophage theory of depression. Medical Hypotheses, 35, 298–306.

    Article  CAS  PubMed  Google Scholar 

  • Song, C, Dinan, T., & Leonard, B. E. (1994). Changes in immunoglobulin, complement and acute phase protein levels in depressed patients and normal controls. Journal of Affective Disorders, 30, 283–288.

    Article  CAS  PubMed  Google Scholar 

  • Song, C, Merali, Z., & Anisman, H. (1998). Variations of nucleus accumbens dopamine and serotonin following systemic interleukin-1, interleukin-2 or interleukin-6 treatment. Neuroscience, in press.

    Google Scholar 

  • Sonti, G., Ilyin, S. E., & Plata-Salaman, C. R. (1996). Anorexia induced by cytokine interactions at patho-physiological concentrations. American Journal of Physiology, 270, R1394–R1402.

    CAS  Google Scholar 

  • Strijbos, P. J. & Rothwell, N. J. (1995). Interleukin-1 beta attenuates excitatory amino acid-induced neurode-generation in vitro: Involvement of nerve growth factor. Journal of Neuroscience, 15, 3468–3478.

    Article  CAS  PubMed  Google Scholar 

  • Suzuki, E., Shintani, F., Kanba, S., Asai, M., & Nakaki, T. (1997). Immobilization stress increases mRNA levels of interleukin-1 receptor antagonist in various brain regions. Cellular Molecular Neurobiology, 17, 557–562.

    Article  CAS  PubMed  Google Scholar 

  • Takao, T., Tojo, C, Nishioka, T, Kurokawa, H., Takemura, T., Hashimoto, K., & De Souza, E. B. (1994). Reciprocal modulation of corticotropin-releasing factor and interleukin-1 receptors following ether-laparotomy stress in the mouse. Brain Research, 660, 170–174

    Article  CAS  PubMed  Google Scholar 

  • Taupin, V., Toulmond, S., Serrano, A., Benavides, J., & Zavala, F. (1993). Increase in IL-6, IL-1, and TNF levels in rat brain following traumatic lesion. Journal of Neuroimmunology, 42, 177–186.

    Article  CAS  PubMed  Google Scholar 

  • Terao, A., Oikawa, M, & Saito, M. (1993). Cytokine-induced change in hypothalamic norepinephrine turnover: involvement of corticotropin-releasing hormone and prostaglandins. Brain Research, 622, 257–261.

    Article  CAS  PubMed  Google Scholar 

  • Tilders, F. J. H., Schmidt, E. D., & De Goeij, D. C. E. (1993). Phenotypic plasticity of CRF neurons during stress. Annals of the New York Academy of Sciences, 697, 39–52.

    Article  CAS  PubMed  Google Scholar 

  • van Dam, A-M., Brouns, M., Louisse, S., & Berkenbosch, F. (1992). Appearance of interleukin-1 in macrophages and in ramified microglia in the brain of endotoxin-treated rats: a pathway for the induction of non-specific symptoms of sickness? Brain Research, 588, 291–296.

    Article  PubMed  Google Scholar 

  • Watkins, L. R., Maier, S. F., & Goehler, L. E. (1995). Cytokine-to-brain communication: A review & analysis of alternative mechanisms. Life Sciences, 11, 1011–1026.

    Article  Google Scholar 

  • Whishaw, I. Q. (1985). Formation of a place learning-set by the rat: a new paradigm for neurobehavioral studies. Physiology & Behavior, 35, 139–143.

    Article  CAS  Google Scholar 

  • Whitnall, M. H., Perlstein, R. S., Mougey, E. H., & Neta, R. (1992). Effects of interleukin-1 on the stress responsive and nonresponsive subtypes of corticotropin-releasing hormone neurosecretory axons. Endocrinology, 131, 37–44.

    Article  CAS  PubMed  Google Scholar 

  • Wise, R. A. (1985). The anhedonia hypothesis: Mark III. Behavioural Brain Science, 8, 178–186.

    Article  Google Scholar 

  • Yabuuchi, K., Sharma, S., Catania, A. P., & Lipton, M. (1996). Induction of interleukin-1β mRNA in the hypothalamus following subcutaneous injections of formalin into the rat hind paws. Neuroscience Letters, 207, 109–112.

    Article  CAS  PubMed  Google Scholar 

  • Yang, Z-J., Koseki, M., Meguid, M. M., Gleason, J. R., & Debonis, D. (1994). Synergistic effect of rhTNF-a and rhIL-la in inducing anorexia in rats. American Journal of Physiology, 36, R1056–R1064.

    Google Scholar 

  • Yirmiya, R. (1996). Endotoxin produces a depressive-like episode in rats. Brain Research, 711, 163–174.

    Article  CAS  PubMed  Google Scholar 

  • Zacharko, R. M. & Anisman, H. (1991). Stressor-provoked alterations of intracranial self-stimulation in the mesocorticolimbic system: An animal model of depression. In P. Willner & J. Scheel-Kruger (Eds.), The Mesolimbic Dopamine System: From Motivation to Action (pp. 411–442). New York: Wiley.

    Google Scholar 

  • Zalcman, S., Green-Johnson, J. M., Murray, L., Nance, D. M., Dyck, D., Anisman, H., & Greenberg, A. (1994). Cytokine-specific central monoamine alterations induced by interleukin (IL)-l, IL-2, and IL-6. Brain Research, 643, 40–9.

    Article  CAS  PubMed  Google Scholar 

  • Zhou, D. H., Shanks, N., Riechman, S. E., Liang, R. M., Kusnecov, A. W, & Rabin, B. S. (1996). Interleukin-6 modulates interleukin-1 and stress-induced activation of the hypothalamic-pituitary-adrenal axis in male rats. Neuroendocrinology, 63, 227–236.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Neuroscience, Carleton University, Ottawa, Canada

    Hymie Anisman

  2. School of Psychology, and Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Canada

    Zul Merali

Authors
  1. Hymie Anisman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zul Merali
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. INRA-INSERM, Bordeaux, France

    Robert Dantzer

  2. CNRS, Paris, France

    Emmanuelle E. Wollman

  3. The Hebrew University of Jerusalem, Jerusalem, Israel

    Raz Yirmiya

Rights and permissions

Reprints and permissions

Copyright information

© 1999 Kluwer Academic/Plenum Publishers

About this chapter

Cite this chapter

Anisman, H., Merali, Z. (1999). Anhedonic and Anxiogenic Effects of Cytokine Exposure. In: Dantzer, R., Wollman, E.E., Yirmiya, R. (eds) Cytokines, Stress, and Depression. Advances in Experimental Medicine and Biology, vol 461. Springer, New York, NY. https://doi.org/10.1007/978-0-585-37970-8_12

Download citation

  • DOI: https://doi.org/10.1007/978-0-585-37970-8_12

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-0-306-46135-4

  • Online ISBN: 978-0-585-37970-8

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation