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2004, Number 3

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Salud Mental 2004; 27 (3)

Interacciones neuroendocrinoinmunológicas

Pavón RL, Hernández ME, Loría SF, Sandoval LG

Language: Spanish
References: 52
Page: 19-25
PDF size: 61.95 Kb.


ABSTRACT

For 20 years, a great number of clinical and experimental evidence have shown the existence of a constant and bi-directional communication between the neuroendocrine system and the immune response, called neuroendocrineimmune (NEI) interactions. These interactions help the homeostasis maintenance to stressful stimuli, whether they are physical or systemic bacterial, viral or parasitical infections, as well as tissular injuries or psychological stress, that is secondary to the individual’s perception and processing.
Stress is a physicochemical or emotional process that induces tension. This process promotes the release of proinflamatory cytokines, hormones such as the corticotrophin-release hormone (CRH) and cortisol, and a wide number of neurotransmitters that are together responsible for some behavioral alterations.
Both systemic and psychological stress elicits an equivalent response in an organism, but acute stressors have effects considered beneficial, while chronic stressors have nocive effects. The adaptative response of the organism to a stressful stimulus consists of an increase of the sera levels of proinflammatory cytokines like tumor necrosis factor-alpha (TNF-α) and interleukine (IL)-1 and IL-6, produced by immune response cells like the lymphocytes and macrophages. When this proinflammatory cytokines reach a 10nM concentration, they bind to their receptors and can stimulate the Central Nervous System (CNS). Although the brain has specific cytokine receptors located in different anatomical regions, the most densely one is the hippocampus. In addition to the existence of a great number of cytokine receptors in the brain, this organ has the capacity to synthesize and secrete in situ a wide variety of cytokines, ability that makes it susceptible of being stimulated by both systemic and in situ produced cytokines.
The activity of the NEI interactions starts when systemic or psychological stressful stimuli lead to the release of proinflammatory cytokines. When these reach a 10nM concentration, they bind to their specific brain receptors, following different neural pathways and a cascade of events is thus triggered: 1) Neuroimmune events initiate the cytokine release within the brain, 2) neurochemical events initiate the release of neurotransmitters, such as norepinephrine (NE) and serotonine (5HT), 3) neuroendocrine events beginning with CRH secretion activate the hipotalamus-pituitary-adrenal (HPA) axis. The activity of the axis finishes when cortisol and anabolic androgens, such as dehydroepiandrosterone (DHEA), are released into the blood stream. All the previous events lead ultimately to 4) behavioral changes known as “sickness behavior”.
Both cortisol and DHEA have specific receptors in almost every cell, particularly those of the immune response like the T lymphocytes, which are highly susceptible to variations in the circulating levels of these molecules. At low concentrations and during short periods of time, cortisol acts as an immunostimulant, especially for a T lymphocyte subset known as T-helper 2 (TH2), involved in the humoral immune response, mainly mediated by antibodies. On the other hand, DHEA positively stimulates the T lymphocyte subset called T-helper 1 (TH1), which favors the cellular immune response.
The difference between TH1 and TH2 lymphocyte subsets lies in the profile of cytokines secreted by each one. TH1 cells secrete proinflammatory cytokines, such as IL-1, TNF-α and IL-6, while TH2 cells secrete antinflammatory cytokines, such as IL-10, IL- 13 and IL-4, that are antagonist to those secreted by TH1 cells. The antagonism between cytokines is an important point of balance for the immune system and the NEI interactions.
Cortisol also has a high density of brain receptors located mainly in the hippocampus. Under normal conditions, when the stressful stimulus disappears, proinflammatory cytokine production decreases and cortisol leads the NEI interactions to the basal condition again.
The long-term presence of stressful stimuli causes the chronic increase of circulating cortisol, resulting in an impairment of the NEI interactions, which can originate infectious, chronic or autoimmune diseases, as well as psychiatric disorders like depression, schizophrenia, Alzheimer’s disease and anorexia.
Every one of us faces a series of systemic and psychological stressful stimuli all through our lives. The intensity and duration of those stimuli will depend on our capacity to cope with them; this capacity is sustained by our genetic background and the learning provided by our social and environmental experiences.
During these last years, the study of the NEI interactions has acquired great interest because the knowledge generated within this area will allow the development of new and efficient therapeutical approaches to improve and control several physical and psychiatric disorders.


REFERENCES

  1. ABBAS A, LICHTMAN AH: Cellular and molecular immunology. WB Sanders Company. Philadelphia, 2000.

  2. ALTAMURA AC, BOIN F, MAES M: HPA axis and cytokines dysregulation in schizophrenia: potential implications for the antipsychotic treatment. Eur Neuropsychopharmacol, 10(1):1- 4, 1999.

  3. ANISMAN H, HAYLEY S, TURRIN N, MERALI Z: Cytokines as a stressor: implications for depressive illness. Int J Neuropsychopharmacol, 5(4):357-73, 2002.

  4. ANISMAN H, MERALI Z, HAYLEY S: Sensitization associated with stressors and cytokine treatments. Brain Behav Immun, 17(2):86-93, 2003.

  5. ANISMAN H, RAVINDRAN AV, GRIFFITHS J, MERALI Z: Endocrine and cytokine correlates of major depression and dysthymia with typical or atypical features. Molecular Psychiatry, 4(2):182-8, 1999.

  6. ASHWELL JD, LU FW, VACCHIO MS: Glucocorticoids in T cell development and function. Annu Rev Immunol, 18:309- 45, 2000.

  7. AXELSON DA, DORAISWAMY PM, MCDONALD WM, BOYKO OB, TUPLER LA y cols.: Hypercortisolemia and hippocampal changes in depression. Psychiatry Research, 47(2):163-73, 1993.

  8. BANKS WA, KASTIN AJ, DURHAM DA: Bidirectional transport of interleukin-1 alpha across the blood brain barrier. Brain Research Bulletin, 23:437-443, 1989.

  9. BERCZI I, CHALMERS IM, NAGY E, WARRINGTON RJ: The immune effects of neuropeptides. Baillieres Clinical Rheumatology, 10(2):227-57, 1996.

  10. BLACK PH: Immune system-central nervous system interactions: effect and immunomodulatory consequences of immune system mediators on the brain. Antimicrob Agents Chemother, 38(1):7-12, 1994.

  11. BREBNER K, HAYLEY S, ZACHARKO R, MERALI Z, ANISMAN H: Synergistic effect of IL-1β, IL-6, and TNF-α; central monoamine, corticosterone, and behavioral variations. Neuropsychopharmacology, 22(6):566-80, 1999.

  12. BREMNER JD: Does stress damage the brain? Biol Psychiatry, 45(7):797-805, 1999.

  13. BROWN ES, RUSH AJ, MCEWEN BS: Hippocampal remodeling and damage by corticosteroids: implication for mood disorders. Neuropsychopharmacology, 21(4):474-84, 1999.

  14. DANTZER R, BLUTHE RM, CASTANON N, CHAUVET N, CAPURON L y cols.: Cytokine effects on behavior. En: Ader R, Felten DL, Cohen N (eds.). Psychoneuroimmunology, 2:703-727, Academic Press, Nueva York, 2001.

  15. DUMAN RS, MALBERG J, THOME J: Neural plasticity to stress and antidepressant treatment. Biol Psychiatry, 46(9):1181-91, 1999.

  16. DUNN AJ, WANG J, ANDO T: Effects of cytokines on cerebral neurotransmission. Comparison with the effects of stress. Advances Experimental Medical Biology, 461:117-27, 1999.

  17. ESKANDARI F, STERNBERG EM: Neural-immune interactions in health and disease. Ann N Y Acad Sci, 966:20- 7, 2002.

  18. ESPOSITO P, GHEORGHE D, KANDERE K, PANG X, CONNOLLY R, JACOBSON S: Acute stress increases permeability of the blood-brain barrier through activation of mast cells. Brain Research, 888:117-127, 2001.

  19. FORGET H, LACROIX A, SOMMA M, COHEN H: Cognitive decline in patients with Cushing´s syndrome. J International Neuropsychology Society, 6(1):20-9, 2000.

  20. FUCHS E, FLUGGE G: Modulation of binding sites for corticotropin-releasing hormone by psychosocial stress. Psychoneuroendocrinology, 20(1):33-51, 1995.

  21. GARCIA-MAURINO S, GONZALEZ-HABA MG, CALVO JR, RAFII-EL-INDRISSI M cols: Melatonin enhances IL-12, IL-6 and INF-gamma production by human circulating CD4+ cells: a possible nuclear receptor-mediated mechanism involving T helper type I lymphocytes and monocytes. J Immunol, 159(2):574-81, 1997.

  22. GUTIERREZ EG, BANKS WA, KASTIN AJ: Murine tumor necrosis factor alpha is transported from blood to brain in the mouse. J Neuroimmunology, 47:169-176, 1993.

  23. HADDAD JJ, SAADE NE, SAFIEH-GARABEDIAN B: Cytokines and neuro-immune-endocrine interactions: a role for the hypothalamic-pituitary-adrenal revolving axis. J Neuroimmunol, 133(1-2):1-19, 2002.

  24. HAYLEY S, MERALI Z, ANISMAN H: Stress and cytokineelicited neuroendocrine and neurotransmitter sensitization: implications for depressive illness. Stress, 6(1):19-32, 2003.

  25. KRONFOL Z, REMICK DG: Cytokines and the brain: implications for clinical psychiatry. Am J Psychiatry, 157(5):683- 94, 2000.

  26. LAYE S, GHESUI G, CREMONA S, COMBE C, KELLY K y cols.: Endogenous brain IL-1 mediates LPS-induced anorexia and hypothalamic cytokine expression. American J Physiol Regul Integr Comp Physiol, 279(1):493-498, 2000.

  27. MAIER SF, WATKINS LR: Cytokines for psychologists: implications of bidirectional immune-to-brain communication for understanding behavior, mood, and cognition. Psichological Review, 105:83-107, 1998.

  28. MARK KS, TRICKLER WJ, MILLER DW: Tumor necrosis factor-alpha induces cyclooxygenase-2 expression and prostaglandin release in brain microvessel endothelial cells. J Pharmacological Experimental Therapeutics, 297:1051-1058, 2001.

  29. MARX C, EHRHART-BORNSTEIN M, SCHERBAUM WA, BORNSTEIN SR: Regulation of adrenocortical function by cytokines-relevance for immune-endocrine interaction. Hormone Metabolism Research, 30(6-7):416-20, 1998.

  30. MATALKA KZ: Neuroendocrine and cytokines-induced responses to minutes, hours, and days of mental stress. Euroendocrinol Lett, 24(5):283-92, 2003.

  31. MCEWEN BS, WINGFIELD JC: The concept of allostasis in biology and biomedicine. Hormones Behavior, 43:2-15, 2003.

  32. MCEWEN BS, GOULD EA, SAKAI RR: The vulnerability of the hippocampus to protective and destructive effects of glucocorticoids in relation to stress. British J Psychiatry (Supl 15):18-23, 1992.

  33. MCEWEN BS, STELLAR E: Stress and the individual. Mechanisms leading to disease. Arch Intern Med, 153(18):2093-101, 1993.

  34. MCEWEN BS: Posible mechanisms for atrophy of the human hippocampus. Molecular Psychiatry, 2(3):255-62, 1997.

  35. MERRIL JE, BENVENISTE EN: Cytokines in inflammatory brain lesions: helpful and harmful. Trends Neuroscience, 8:331-338, 1996.

  36. NUSSDORFER GG, MAZZOCCHI G: Immune-endocrine interactions in the mammalian adrenal gland: facts and hypotheses. International Review Cytology, 183:143-84, 1988.

  37. OHL F, MICHAELIS T, VOLLMANN-HONSDORF K, KIRSCHBAUM C, FUCHS E: Effects of chronic psychosocial stress and long-term cortisol treatment on hippocampusmediated momory and hippocampal volume: a pilot-study in tree shrews. Psychoneuroendocrinology, 25(4):357-63, 2000.

  38. PROLO P, LICINIO J: Cytokines in affective disorders and schizophrenia: new clinical and genetic findings. Mol Psychiatry, 4(4):396, 1999.

  39. QUAGLIARELLO VJ, WISPLWEY B, LONG WJ Jr, SHELD WM: Recombinant interleukin-1 induces meningitis and blood-brain barrier injury in the rat. J Clinical Investigations, 87:1360-1366, 1991.

  40. ROOK GA: Glucocorticoids and immune function. Baillieres Best Practical Research Clinical Endocrinology Metabolism, 13(4):567-81, 1999.

  41. SHELINE YI, SANGHAVI M, MINTUM MA, GADO MH: Depression duration but not age predicts hippocampal volume loss in medically healthy women with recurrent major depression. J Neuroscience, 19(12):5034-43, 1999.

  42. SHERIDAN JF, DOBBS C, JUNG J, CHU X, KONSTANTINOS A y cols.: Stress-induced neuroendocrine modulation of viral pathogenesis and immunity. Ann N Y Acad Sci, 1(840):803-8, 1998.

  43. STEFFENS DC, BYRUM CE, MCQUOID DR, GREENBERG DL, PAYNE ME y cols.: Hippocampal volume in geriatric depression. Biol Psychiatry, 48(4):301-9, 2000.

  44. STERNBERG EM: Interactions between the immune and neuroendocrine systems. Prog Brain Res, 122:35-42, 2000.

  45. STERNBERG EM: The Balance Within: The Science Connecting Health and Emotions. W.H. Freeman & Co. Nueva York, 2000.

  46. STOKES PE: The potential role of excessive cortisol induced by HPA hyperfunction in the pathogenesis of depression. European Neuropsychopharmacology, (5 Supl):77-82, 1995.

  47. SZELENYI J: Cytokines and the central nervous system. Brain Res Bull, 54(4):329-38, 2001.

  48. TURNBULL AV, RIVIER C: Regulation of the HPA axis by cytokines. Brain, Behavior Immunology, 9(4):253-75, 1995.

  49. WATKINS LR, MAIER SF, GOEHLER LE : Cytokine-tobrain communication: a review, analysis of alternative mechanisms. Life Science, 11:1011-1026, 1995.

  50. WHEELER MD, IKEJEMA K, ENOMOTO N, STACKLEWITZ RF, SEABRA V y cols.: Glycine: a new anti-inflammatory immunonutrient. Cell Mol Life Sci, 56(9- 10):843-56, 1999.

  51. WILDER RL, GRIFFITHS MM, CANNON GW, CASPI R, GULKO PS y cols.: Genetic factors involved in central nervous system/immune interactions. Adv Exp Med Biol, 493:59-67, 2001.

  52. WILLIAM EP: Fundamental immunology. Lippincott-Raven Publishers. Cuarta edición, Philadelphia, 1999.




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