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Immunosensory Signaling: Role of Cytokines

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Book cover Cytokines and Mental Health

Part of the book series: Neurobiological Foundation of Aberrant Behaviors ((NFAB,volume 7))

Abstract

Traditional conceptualizations of neural-immune interactions focused on mechanisms by which the brain modulates immune functions, for instance how stress, and/or personality variables can affect immune function. However, it is now well established that the converse is also true: immune activation, following infection or during neoplastic or autoimmune conditions, exerts profound influences upon brain function. Thus, neural- immune interactions are bi-directional.

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References

  1. Reichenberg, A., R., Yirmiya, A., Schuld, T., et al. Cytokine-associated emotional and cognitive disturbances in humans. Arch. Gen. Psychiatry 2001; 58:445–452.

    Article  PubMed  CAS  Google Scholar 

  2. Lyte, M., Varcoe, J.J. and Bailey M.T. Anxiogenic effect of subclinical bacterial infection in mice in the absence of overt immune activation. Physiol. Behav. 1998; 65:63–69.

    Article  PubMed  CAS  Google Scholar 

  3. Goehler, L.E., Gaykema, R.P.A., Hansen, M.K., et al. Vagally mediated fever: a visceral chemosensory modality. Auton. Neurosci., 2000; 85:49–59

    Article  PubMed  CAS  Google Scholar 

  4. Janeway, C.A. and Travers, P. Immunobiology: The Immune System in Health and Disease. London: Current Biology Ltd./Garland Publishing, 1997, 7:26.

    Google Scholar 

  5. Rothwell, N.J., Luheshi, G. and Toulmond, S. Cytokines and their receptors in the central nervous sytem: Physiology, pharmacology, and pathology. Pharmacol. Ther. 1996; 69:85–95.

    Article  PubMed  CAS  Google Scholar 

  6. Laye, S., Gheusi, G., Cremona, S., et al. Endogenous brain IL-1 mediates LPS-induced anorexia and hypothalamic cytokine expression. Am. J. Physiol. 2000; 279:R93-R98.

    CAS  Google Scholar 

  7. Krueger, J.M., Fang, J., Taishi, P., et al. Sleep: a physiologic role for IL-1β and TNF-a. Ann. N.Y. Acad. Sci. 1998; 856:148–159

    Article  PubMed  CAS  Google Scholar 

  8. Abbas, A.K., Murphy, K.M. and Sher, A. Functional diversity of helper T lymphocytes. Nature, 1996; 383:787–793.

    Article  PubMed  CAS  Google Scholar 

  9. Cartmell, T., Luheshi, G.N., Hopkins, S.J., et al. Role of endogenous interleukin-1 receptor antagonist in regulating fever induced by localised inflammation in the rat. J. Physiol. 2001; 531:171–180.

    Article  PubMed  CAS  Google Scholar 

  10. Banchereau, J. and Steinman, R.M. Dendritic cells and the control of immunity, Nature 1998; 392:245–252.

    Article  PubMed  CAS  Google Scholar 

  11. Kopp, E.B. and Medzhitov, R. The Toll-receptor family and control of innate immunity. Curr. Opin. Immunol. 1999; 11:13–18.

    Article  PubMed  CAS  Google Scholar 

  12. Medzhitov, R. and Janeway, C.A. Innate immunity: impact of the adaptive immune response. Curr. Opin. Immunol. 1997; 9:4–9.

    Article  PubMed  CAS  Google Scholar 

  13. Reis e Sousa, C., Sher, A. and Kaye, P. The role of dendritic cells in the induction and regulation of immunity to microbial infection. Curr. Opin. Immunol. 1999; 11:392–399.

    Article  PubMed  CAS  Google Scholar 

  14. Steinman, R.M. The dendritic cell and its role in immunogenicity. Ann. Rev. Immunol. 1991;9:271–296.

    Article  CAS  Google Scholar 

  15. Van Dam, A.M.W., Brouns, M., Louisse, S., et al. Appearance of interleukin-1 in macrophages and ramified microglia in the brain of endotoxin-treated rats: a pathway for the induction of non-specific symptoms of sickness? Brain Res. 1992; 588:291–296.

    Article  PubMed  Google Scholar 

  16. Goehler, L.E., Gaykema, R.P.A., Nguyen, K.T., et al. Interleukin-1β in immune cells of the abdominal vagus nerve: an immune to nervous system link? J. Neurosci. 1999b; 17: 2799–2806.

    Google Scholar 

  17. Chen, G. and Reichlin, S. Clearance of [125I]-tumot necrosis factor-a from the brain into the blood after intracerebroventricular injection in rats. NeurolmmunoModulation 1998; 5:261–269.

    Article  CAS  Google Scholar 

  18. Dickstein, J.B., Moldovsky, H., Lue F.A., et al. Intracerebroventricular injection of TNF-αpromotes sleep and is recovered in cervical lymph. Am. J. Physiol. 1999; 276:R1018-R1022.

    PubMed  CAS  Google Scholar 

  19. Di Santo, E., Benigni, F., Agnello, D., et al. Peripheral effects of centrally administered interleukin-1b in mice in relation to its clearance from the brain into the blood and tissue distribution. Neuroimmunomodulation 1999; 6:300–304.

    Article  PubMed  Google Scholar 

  20. Ek, M., Engblom, D., Sana, S., et al. Inflammatory response: pathway across the blood-brain barrier. Nature 2001; 410:430–431.

    Article  PubMed  CAS  Google Scholar 

  21. Herkenham, M., Lee, H. Y. and Baker, R.A. Temporal and spatial patterns of c-fos mRNA induced by intravenous interleukin-1: A cascade of non-neuronal cellular activation at the blood brain barrier. J. Comp. Neurol. 1998; 400:175–196.

    Article  PubMed  CAS  Google Scholar 

  22. Lee, H.Y., Whiteside, M.B. and Herkenham, M. Area postrema removal abolishes stimulatory effects of intravenous interleukin-1β on hypothalamic-pituitary-adrenal axis activity and c-fos mRNA in the hypothalamic paraventricular nucleus. Brain Res. Bull. 1998; 46:495–503.

    Article  PubMed  CAS  Google Scholar 

  23. Saper, C.B. and Breder, C.D. The neurological basis of fever N. Engl. J. Med. 1994; 330:1880–1886.

    Article  PubMed  CAS  Google Scholar 

  24. Day, H.E.W. and Akil, H. Differential pattern of c-fos mRNA in rat brain following central and systemic administration of interleukin-1-beta: Implications for mechanism of action. Neuroendocrinol. 1996; 63:207–218.

    Article  CAS  Google Scholar 

  25. Ericsson, A., Kovacs, K. J. and Sawchenko, P.E. A functional neuroanatomical analysis of central pathways subserving the effects of interleukin-1 on stress-related neuroendocrine neurons. J. Neurosci. 1994; 14: 897–813.

    PubMed  CAS  Google Scholar 

  26. Valleires, L. and Rivest, S. Regulation of the genes encoding interleukin-6, its receptor, and gpl30 in the rat brain in response to the immune activator lipopolysaccharide and the pro-inflamatory cytokine interleukin-1 beta. J. Neurochem. 1997; 69:1668–1683.

    Article  Google Scholar 

  27. Vernet-der Gerabedian, B., Lemaigre-Dubreuil, Y. and Mariani, J. Central origin of IL- 1β produced during peripheral inflammtion: role of meninges. Mol. Brain Res. 2000; 75:259–263

    Article  Google Scholar 

  28. Quan, N., Stern, E.L., Whiteside, M.B., et al. Induction of pro-inflammatory cytokine mRNAs in the brain afterperipheral injection of subseptic doses of lipopolysaccharide in the rat. J. Neuroimmunol. 1999; 93: 72–80

    Article  PubMed  CAS  Google Scholar 

  29. Ek, M., Arias, C., Sawchenko, P., et al. Distribution of the EP3 prostaglandin E2 receptor subtype in the rat brain: relationship to sites of interleukin-1-induced cellular responsiveness. J. Comp. Neurol. 2000; 428:5–20.

    Article  PubMed  CAS  Google Scholar 

  30. Ericsson, A., Arias, C. and Sawchenko, P.E. Evidence for an intramedullary prostaglandin-dependent mechanism in the activation of stress-related neuroendocrine circuitry by intravenous interleukin-1. J. Neurosci. 1997; 17:7166–7179.

    PubMed  CAS  Google Scholar 

  31. Matsumura, K., Kaihatsu, S., Imai, H., et al. Cyclooxygenase in the vagal afferents: is it involved in the brain prostaglandin response evoked by lipopolysaccharide? Auton. Neurosci. 2000; 85:88–92

    Article  PubMed  CAS  Google Scholar 

  32. Scammell, T.E., Elmquist, J.K., Griffin, J.D., et al. Ventromedial preoptic prostaglandin E2 activates fever-producing autonomic pathways. J. Neurosci. 1996; 16:6246–6254.

    PubMed  CAS  Google Scholar 

  33. Milligan, E., McGorry, M.M., Fleshner, M., et al. Subdiaphragmatic vagotomy does not prevent fever following intracerebroventricular prostaglandin: further evidence for the importance of vagal afferents in immune-to-brain communication. Brain Res. 1997; 766:240–243

    Article  PubMed  CAS  Google Scholar 

  34. Sugimoto, N., Simons, C.T. and Romanovsky, A.A. Vagotomy does not affect thermal responsiveness to intrabrain prostaglandin E2 and cholecystokinin octapeptide. Brain Res. 1999;844:157–163.

    Article  PubMed  CAS  Google Scholar 

  35. Zhang, J. and Rivest, S. A functional analysis of EP4 receptor-expressing neurons in mediating the action of prostaglandin E2 within specific nuclei of the brain in response to circulating interleukin-1β. J. Neurochem. 2000; 74:2134–2145.

    Article  PubMed  CAS  Google Scholar 

  36. Banks, W.A., Ortiz, L., Lotkin, S.R., et al. Human interleukin (IL) lα, murine, IL-1α, and murine IL-1β are transorted from the blood to the brain by a shared saturable mechanism. J. Pharmacol. Exp. Therap. 1994; 259:988–996.

    Google Scholar 

  37. Luheshi, G.N., Gay, J. and Rothwell, N.J. Circulating IL-6 is transported into the brain via a saturable transport mechanismin the rat. Br. J. Pharm. 1996; 111:146P.

    Google Scholar 

  38. Romeo, H.E., Tio, D.L., Rahman, S.U., et al. The glossopharyngeal nerve as a novel pathway in immune-to-brain communication: relevance to neuroimmune surveillance of the oral cavity. J. Neuroimmunol. 2001; 115:91–100.

    Article  PubMed  CAS  Google Scholar 

  39. Kobierski, L. A., Srivastava, S. and borsook, D. Systemic lipopolysaccharide and interleukin-1β activate the interleukin 6: STAT intracellular signaling pathqay in neurons of mouse trigeminal ganglion. Neurosci. Lett. 2000; 281:61–64

    Article  PubMed  CAS  Google Scholar 

  40. Berthoud, H.-R. and Neuhuber, W.L Functional and chemical anatomy of the afferent vagal system. Autonom. neuroses. Basic Clin. 2000; 85:1–17.

    Article  CAS  Google Scholar 

  41. Felton, D.L., Livnat, S., Felton, S.Y., et al. Sympathetic innervation of lymph nodes in mice. Brain Res. Bull 1984; 13:693–696.

    Article  Google Scholar 

  42. Fink, T. and Weihe, E. Multiple neuropeptides in nerves supplying mammalian lymph nodes: messenger candidates for sensory and autonomic neuroimmunomodulation. Neurosci. Lett. 1988; 19:39–44.

    Article  Google Scholar 

  43. Popper, P., Mantyh, C.R., Vigna, S.R., et al. The localization of sensory nerve fibers and receptor binding sites for sensory neuropeptides in canine lymph nodes. Peptides 1988; 9:257–267.

    Article  PubMed  CAS  Google Scholar 

  44. Reudl, C., Reiser, C., Bock, G., et al. Phenotypic and functional characterization of CDllc+ dendritic cell population in mouse Peyer’s patches. Eur. J. Immunol. 1996; 26:1801–1806.

    Article  Google Scholar 

  45. Watkins, L.R., Weirtelak, E.P., Goehler, L.E., et al. Characterization of cytokine induced hyperalgesia. Brain Res. 1994;654:15–26

    Article  PubMed  CAS  Google Scholar 

  46. Watkins, L.R., Goehler, L.E., Relton, J., et al. Immune-to-brain communication: Systemic tumour necrosis factor-alpha (TNF-alpha) produces behavioral hyperalgesia via vagal afférents. Brain Res. 1995; 692:244–250.

    Article  PubMed  CAS  Google Scholar 

  47. Watkins, L.R., Goehler, L.E., Relton, J.K., et al. Blockade of interleukin-1-induced fever by subdiaphragmatic vagotomy: evidence for vagal mediation of immune-brain communication. Neurosci. Lett. 1995; 183:27–31.

    Article  PubMed  CAS  Google Scholar 

  48. Romanovsky, A.A., Simons, C.T., Szekely, M., et al. The vagus nerve in the thermoregulatory response to systemic inflammation. Am. J. Physiol. 1997; 273:R407- R413.

    PubMed  CAS  Google Scholar 

  49. Sehic, E. and Blatteis, C.M. Blockade of lipopolysaccharide-induced fever by subdiaphragmatic vagotomy in guinea pigs. Brain Res. 1996; 726:160–166.

    Article  PubMed  CAS  Google Scholar 

  50. Hansen, M.K. and Kreuger, J.M. Subdiaphragmatic vagotomy blocks the sleep- and fever- promoting effects of interleukin-1β. Am. J. Physiol. 1997; 273:R1246-R1253.

    PubMed  CAS  Google Scholar 

  51. Fleshner, M., Goehler, L.E., Hermann, J., et al. Interleukin 1β induced corticosterone elevation and hypothalamic NE depletion is vagally mediated. Brain Res. Bull. 1995; 37:605–610.

    Article  PubMed  CAS  Google Scholar 

  52. Gaykema, R.P.A., Dijkstra, I. and Tilders, F.J.H. Subdiaphragmatic vagotomy suppresses endotoxin-induced activation of the hypothalamic corticotropin-releasing hormones neurons and ACTH secretion. Endocrinol. 1995; 136:4717–4720.

    Article  CAS  Google Scholar 

  53. Kapcala, L.P., He, J.R., Gao, Y., et al. Subdiaphragmatic vagotomy inhibits intra- abdominal interleukin-1β stimulation of adrenocorticotropin secretion. Brain Res. 1996; 728:247–254

    Article  PubMed  CAS  Google Scholar 

  54. Goehler, L.E., Busch, C.R., Tartaglia, N., et al. Blockade of cytokine induced conditioned taste aversion by subdiaphramatic vagotomy: further evidence for vagal mediation of immune-brain interactions. Neurosci. Lett. 1995; 185:163–166.

    Article  PubMed  CAS  Google Scholar 

  55. Bluthe, R.-M., Walter, V., Parnet, P., et al. Lipopolysaccharide induces sickness behavior in rats by a vagal mediated mechanism. CR. Acad. Sci. Paris 1994; 317:499–503.

    CAS  Google Scholar 

  56. Hansen, M.K., O’Conner, K.A., Goehler, L.E., et al. The role of the vagus nerve in interleukin-1β-induced fever is dependent on dose. Am. J. Physiol. 2001; 280:R929- R934.

    CAS  Google Scholar 

  57. Van Dam, A.M.W., Bol, J.G.J.M., Gaykema, R.P.A., et al. Vagotomy does not inhibit high dose LPS-induced interleukin-1β immunoreactivity in rat brain and pituitary gland. Neurosc. Lett. 2000; 285:169–172.

    Article  Google Scholar 

  58. Romanovsky, A.A. Thermoregulatory manifestations of system inflammation: lessons from vagotomy. Auton. Neurosci. Basic Clin. 2000; 85:39–48.

    Article  CAS  Google Scholar 

  59. Hansen, M.K., Nguyen, K.T., Fleshner, M., et al. Effects of vagotomy on circulating levels of endotoxin, pro-inflammatory cytokines, and corticosterone following intraperitoneal lipoplysaccharide. Am. J. Physiol. 2000; 278:R331-R336.

    CAS  Google Scholar 

  60. Gaykema, R.P.A., Goehler, L.E., Hansen, M.K., et al. Subdiaphragmatic vagotomy blocks interleukin-1β-induced fever but does not reduce interleukin-1β levels in the circulation. Auton. Neurosci. Basic Clin. 2000; 85:72–77.

    Article  CAS  Google Scholar 

  61. Ek, M., Kurosawa, M., Lundeberg, T., et al. Activation of vagal afférents after intravenous injection of interleukin-1β: role of endogenous prostaglandins. J. Neurosci. 1998; 18:9471–9479.

    PubMed  CAS  Google Scholar 

  62. Goehler, L.E., Gaykema, R.P.A., Hammack, S.E., et al. Interleukin-1 induces c-Fos immunoreactivity in primary afferent neurons of the vagus nerve. Brain Res. 1998; 804:306–310.

    Article  PubMed  CAS  Google Scholar 

  63. Niijima, A. The afferent discharges from sensors for interleukin-1β in the hepatoportal system in the anesthetized rat. J. Auton. Nerv. Syst. 1996; 61:287–291

    Article  PubMed  CAS  Google Scholar 

  64. Gaykema, R.P.A., Goehler, L.E., Tilders, F. J. H., et al. Bacterial endotoxin induces Fos immunoreactivity in primary afferent neurons of the vagus nerve. NeuroImmunoMod. 1998; 5:234–240.

    Article  CAS  Google Scholar 

  65. Shurin, G., Shanks, N., Nelson, L., et al. Hypothalamic-pituitary-adrenal activation by the bacterial superantigen staphylococcal enterotoxin B: role of macrophages and T cells. Neuroendocrinol. 1997;65:18–28.

    Article  CAS  Google Scholar 

  66. Litton, M.J., Sander, B., Murphy, E., et al. Early expression of cytokines in lymph nodes after treatment in vivo with Staphyolococcus enterotoxin B. J. Immunol. Meth. 1994; 175:47–58.

    Article  CAS  Google Scholar 

  67. Goehler, L.E., Relton, J.K., Dripps, D., et al. Vagal paraganglia bind biotinylated interleukin-1 receptor antagonist: A possible mechanism for immune-to-brain communication. Brain Res. Bull. 1997;43:357–364.

    Article  PubMed  CAS  Google Scholar 

  68. Adriaensen, D., Timmermans, J.-P., Brouns, I., et al. Pulmonary intraepithelial vagal nodose afferent nerve terminals are confined to neuroepithelial bodies: an anterograde tracing and confocal microscopy study in adult rats. Cell Tiss. Res. 1998; 293:395–405.

    Article  CAS  Google Scholar 

  69. Matsuura, S. Chemoreceptor properties of glomus tissue found in the carotid region of the cat. J. Physiol Lond. 1973; 235:57–73.

    PubMed  CAS  Google Scholar 

  70. Schaffar, N., Roa, H., Kessler, J.P., et al. Immunohistochemical detection of glutamate in rat vagal sensory neurons. Brain Res. 1997; 778:302–308.

    Article  PubMed  CAS  Google Scholar 

  71. Mascarucci, P., Perego, C., Terrazzino, S., et al. Glutamate release in the nucleus tractus solitarius induced by peripheral lipopolysaccharide and interleukin-1β. Neurosci. 1998; 86:1285–1290.

    Article  CAS  Google Scholar 

  72. Wan, W., Wetmore, L., Sorensen, C. M., et al. Neural and biochemical mediators of endotoxin and stress-induced c-fos expression in the rat brain. Brain Res. Bull. 1994; 34:7–14.

    Article  PubMed  CAS  Google Scholar 

  73. Robertson, B., Kong, G., Peng, Z., et al. Interferon-gamma-responsive neuronal sites in the normal rat brain: receptor protein distribution and cell activation revealed by Fos induction. Brain Res. Bull. 2000; 52:61–74.

    Article  PubMed  CAS  Google Scholar 

  74. Wei, Y.P., Kita, M., Shimura, K., et al. Expression of IFN-gamma in cerebrovascular endothelial cells from aged mice. J. Interferon Cytokine Res. 2000; 20:403–409.

    Article  PubMed  CAS  Google Scholar 

  75. Leon, L.R., Kozak, W., Rudolph, K., et al. An antipyretic role for interleukin-10 in LPS fever in mice. Am. J. Physiol. 1999; 276.R81-R89.

    PubMed  CAS  Google Scholar 

  76. Kushikata, T., Fang, J., Wang, Y., et al. Interleukin-4 inhibits spontaneous sleep in rabbits. Am. J. Physiol. 1998; 275:R1185-R1191.

    PubMed  CAS  Google Scholar 

  77. Kushikata, T., Fang, J. and Krueger, J.M. Interleukin-10 inhibits spontaneous sleep in rabbits. J. Interferon Cytokine Res. 1999; 19:1025–1030.

    Article  PubMed  CAS  Google Scholar 

  78. Kubota, T., Fang, J., Kushikata, T., et al. Interleukin-13 and transforming growth factor- beta 1 inhibit spontaneous sleep in rabbits. Am. J. Physiol. 2000; 279:R786-R792.

    CAS  Google Scholar 

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Goehler, L.E. (2003). Immunosensory Signaling: Role of Cytokines . In: Kronfol, Z. (eds) Cytokines and Mental Health. Neurobiological Foundation of Aberrant Behaviors, vol 7. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0323-1_2

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  • DOI: https://doi.org/10.1007/978-1-4615-0323-1_2

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