Skip to main content
The Yale Journal of Biology and Medicine logoLink to The Yale Journal of Biology and Medicine
. 1990 Mar-Apr;63(2):133–146.

Neuromodulative actions of cytokines.

C M Blatteis 1
PMCID: PMC2589308  PMID: 2205054

Abstract

Interleukin 1, interferon alpha 2, and tumor necrosis factor alpha are cytokines that centrally mediate various reactions typical of the host defense responses to infection. The preoptic-anterior hypothalamus is an important, but not exclusive, integrative and controlling region for several of these effects. Although these cytokines display some common functional activities (e.g., pyrogenicity, somnogenicity), the characteristics of the responses they induce are different. Their effects, moreover, can be evoked or suppressed selectively, indicating that the neuronal substrates and/or neuromodulators used are distinct, each possessing discrete but partially overlapping sensory combinations. Nevertheless, it is not yet obvious how these systems are organized and integrated in host defense. It is also unclear whether these cytokines are elaborated peripherally and gain access to the brain or whether they are induced centrally. The available data suggest that circulating cytokines probably do not penetrate the brain but may activate elements in the organum vasculosum laminae terminalis. This site appears to be critically important for the production of the centrally mediated effects of blood-borne cytokines; it is speculated that the cytokines evoke there local signals that transduce their message; serotonin may be linked to these signals.

Full text

PDF
133

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. ATKINS E. Pathogenesis of fever. Physiol Rev. 1960 Jul;40:580–646. doi: 10.1152/physrev.1960.40.3.580. [DOI] [PubMed] [Google Scholar]
  2. Adler M. W., Geller E. B., Rosow C. E., Cochin J. The opioid system and temperature regulation. Annu Rev Pharmacol Toxicol. 1988;28:429–449. doi: 10.1146/annurev.pa.28.040188.002241. [DOI] [PubMed] [Google Scholar]
  3. Ahmed M. S., Llanos-Q J., Dinarello C. A., Blatteis C. M. Interleukin 1 reduces opioid binding in guinea pig brain. Peptides. 1985 Nov-Dec;6(6):1149–1154. doi: 10.1016/0196-9781(85)90442-5. [DOI] [PubMed] [Google Scholar]
  4. Ahokas R. A., Seydoux J., Llanos-Q J., Mashburn T. A., Jr, Blatteis C. M. Hypothalamic opioids and the acute-phase glycoprotein response in guinea pigs. Brain Res Bull. 1985 Dec;15(6):603–608. doi: 10.1016/0361-9230(85)90210-2. [DOI] [PubMed] [Google Scholar]
  5. Atkins E. Fever: its history, cause, and function. Yale J Biol Med. 1982 May-Aug;55(3-4):283–289. [PMC free article] [PubMed] [Google Scholar]
  6. Banet M., Brandt S., Hensel H. The effect of continuously cooling the hypothalamic preoptic area on antibody titre in the rat. Experientia. 1982 Aug 15;38(8):965–966. doi: 10.1007/BF01953680. [DOI] [PubMed] [Google Scholar]
  7. Banet M., Brandt S. The effect of a fever-like response on the secondary antibody response of the rat. Brain Res Bull. 1987 Feb;18(2):265–267. doi: 10.1016/0361-9230(87)90200-0. [DOI] [PubMed] [Google Scholar]
  8. Banet M., Fischer D., Hartmann K. U., Hensel H., Hilling U. The effect of whole body heat exposure and of cooling the hypothalamus on antibody titre in the rat. Pflugers Arch. 1981 Jul;391(1):25–27. doi: 10.1007/BF00580689. [DOI] [PubMed] [Google Scholar]
  9. Benedek G., Obál F., Jr, Szekeres L., Obál F. Two separate synchronizing mechanisms in the basal forebrain: study of the synchronizing effects of the rostral hypothalamus, preoptic region and olfactory tubercle. Arch Ital Biol. 1979 Apr;117(2):164–185. [PubMed] [Google Scholar]
  10. Berkenbosch F., van Oers J., del Rey A., Tilders F., Besedovsky H. Corticotropin-releasing factor-producing neurons in the rat activated by interleukin-1. Science. 1987 Oct 23;238(4826):524–526. doi: 10.1126/science.2443979. [DOI] [PubMed] [Google Scholar]
  11. Bernardini G. L., Richards D. B., Lipton J. M. Antipyretic effect of centrally administered CRF. Peptides. 1984 Jan-Feb;5(1):57–59. doi: 10.1016/0196-9781(84)90051-2. [DOI] [PubMed] [Google Scholar]
  12. Bernheim H. A. Is prostaglandin E2 involved in the pathogenesis of fever? Effects of interleukin-1 on the release of prostaglandins. Yale J Biol Med. 1986 Mar-Apr;59(2):151–158. [PMC free article] [PubMed] [Google Scholar]
  13. Bernton E. W., Beach J. E., Holaday J. W., Smallridge R. C., Fein H. G. Release of multiple hormones by a direct action of interleukin-1 on pituitary cells. Science. 1987 Oct 23;238(4826):519–521. doi: 10.1126/science.2821620. [DOI] [PubMed] [Google Scholar]
  14. Besedovsky H., del Rey A. Neuroendocrine and metabolic responses induced by interleukin-1. J Neurosci Res. 1987;18(1):172–178. doi: 10.1002/jnr.490180124. [DOI] [PubMed] [Google Scholar]
  15. Blalock J. E. A molecular basis for bidirectional communication between the immune and neuroendocrine systems. Physiol Rev. 1989 Jan;69(1):1–32. doi: 10.1152/physrev.1989.69.1.1. [DOI] [PubMed] [Google Scholar]
  16. Blalock J. E., Smith E. M. Human leukocyte interferon (HuIFN-alpha): potent endorphin-like opioid activity. Biochem Biophys Res Commun. 1981 Jul 30;101(2):472–478. doi: 10.1016/0006-291x(81)91284-5. [DOI] [PubMed] [Google Scholar]
  17. Blatteis C. M., Banet M. Autonomic thermoregulation after separation of the preoptic area from the hypothalamus in rats. Pflugers Arch. 1986 May;406(5):480–484. doi: 10.1007/BF00583370. [DOI] [PubMed] [Google Scholar]
  18. Blatteis C. M., Bealer S. L., Hunter W. S., Llanos-Q J., Ahokas R. A., Mashburn T. A., Jr Suppression of fever after lesions of the anteroventral third ventricle in guinea pigs. Brain Res Bull. 1983 Nov;11(5):519–526. doi: 10.1016/0361-9230(83)90124-7. [DOI] [PubMed] [Google Scholar]
  19. Blatteis C. M., Hales J. R., McKinley M. J., Fawcett A. A. Role of the anteroventral third ventricle region in fever in sheep. Can J Physiol Pharmacol. 1987 Jun;65(6):1255–1260. doi: 10.1139/y87-200. [DOI] [PubMed] [Google Scholar]
  20. Blatteis C. M., Hunter W. S., Llanos J., Ahokas R. A., Mashburn T. A., Jr Activation of acute-phase responses by intrapreoptic injections of endogenous pyrogen in guinea pigs. Brain Res Bull. 1984 Jun;12(6):689–695. doi: 10.1016/0361-9230(84)90149-7. [DOI] [PubMed] [Google Scholar]
  21. Blatteis C. M., Hunter W. S., Wright J. M., Ahokas R. A., Llanos-Q J., Mashburn T. A., Jr Thermoregulatory responses of guinea pigs with anteroventral third ventricle lesions. Can J Physiol Pharmacol. 1987 Jun;65(6):1261–1266. doi: 10.1139/y87-201. [DOI] [PubMed] [Google Scholar]
  22. Blatteis C. M., Necker R., Hales J. R., Fawcett A. A., Hirata K. Thermoregulatory responses of febrile sheep to spinal and hypothalamic heating. Am J Physiol. 1987 Dec;253(6 Pt 2):R868–R876. doi: 10.1152/ajpregu.1987.253.6.R868. [DOI] [PubMed] [Google Scholar]
  23. Blatteis C. M., Smith K. A. Hypothalamic sensitivity to leukocytic pyrogen of adult and new-born guinea-pigs. J Physiol. 1979 Nov;296:177–192. doi: 10.1113/jphysiol.1979.sp012998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Boulant J. A., Silva N. L. Interactions of reproductive steroids, osmotic pressure, and glucose on thermosensitive neurons in preoptic tissue slices. Can J Physiol Pharmacol. 1987 Jun;65(6):1267–1273. doi: 10.1139/y87-202. [DOI] [PubMed] [Google Scholar]
  25. Brandt S., Banet M. The effect of hypothalamic temperature on the immune response in the rat. Brain Res Bull. 1984 Aug;13(2):247–251. doi: 10.1016/0361-9230(84)90124-2. [DOI] [PubMed] [Google Scholar]
  26. Breder C. D., Dinarello C. A., Saper C. B. Interleukin-1 immunoreactive innervation of the human hypothalamus. Science. 1988 Apr 15;240(4850):321–324. doi: 10.1126/science.3258444. [DOI] [PubMed] [Google Scholar]
  27. Burch R. M., Connor J. R., Axelrod J. Interleukin 1 amplifies receptor-mediated activation of phospholipase A2 in 3T3 fibroblasts. Proc Natl Acad Sci U S A. 1988 Sep;85(17):6306–6309. doi: 10.1073/pnas.85.17.6306. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. CHOWERS I., HAMMEL H. T., STROMME S. B., MCCANN S. M. COMPARISON OF EFFECT OF ENVIRONMENTAL AND PREOPTIC COOLING ON PLASMA CORTISOL LEVELS. Am J Physiol. 1964 Sep;207:577–582. doi: 10.1152/ajplegacy.1964.207.3.577. [DOI] [PubMed] [Google Scholar]
  29. Cannon J. G., Tatro J. B., Reichlin S., Dinarello C. A. Alpha melanocyte stimulating hormone inhibits immunostimulatory and inflammatory actions of interleukin 1. J Immunol. 1986 Oct 1;137(7):2232–2236. [PubMed] [Google Scholar]
  30. Carr D. B., Bergland R., Hamilton A., Blume H., Kasting N., Arnold M., Martin J. B., Rosenblatt M. Endotoxin-stimulated opioid peptide secretion: two secretory pools and feedback control in vivo. Science. 1982 Aug 27;217(4562):845–848. doi: 10.1126/science.6285473. [DOI] [PubMed] [Google Scholar]
  31. Chowers I., Hammel H. T., Eisenman J., Abrams R. M., McCann S. M. Comparison of effect of environmental and preoptic heating and pyrogen on plasma cortisol. Am J Physiol. 1966 Mar;210(3):606–610. doi: 10.1152/ajplegacy.1966.210.3.606. [DOI] [PubMed] [Google Scholar]
  32. Chowers I., Hammel H. T., Eisenman J., Abrams R. M., McCann S. M. Comparison of effect of environmental and preoptic heating and pyrogen on plasma cortisol. Am J Physiol. 1966 Mar;210(3):606–610. doi: 10.1152/ajplegacy.1966.210.3.606. [DOI] [PubMed] [Google Scholar]
  33. Clark W. G., Harris N. F. Naloxone does not antagonize leukocytic pyrogen. Eur J Pharmacol. 1978 Jun 1;49(3):301–304. doi: 10.1016/0014-2999(78)90106-1. [DOI] [PubMed] [Google Scholar]
  34. Coceani F., Bishai I., Lees J., Sirko S. Prostaglandin E2 and fever: a continuing debate. Yale J Biol Med. 1986 Mar-Apr;59(2):169–174. [PMC free article] [PubMed] [Google Scholar]
  35. Coceani F., Lees J., Bishai I. Further evidence implicating prostaglandin E2 in the genesis of pyrogen fever. Am J Physiol. 1988 Mar;254(3 Pt 2):R463–R469. doi: 10.1152/ajpregu.1988.254.3.R463. [DOI] [PubMed] [Google Scholar]
  36. Coceani F., Lees J., Dinarello C. A. Occurrence of interleukin-1 in cerebrospinal fluid of the conscious cat. Brain Res. 1988 Apr 19;446(2):245–250. doi: 10.1016/0006-8993(88)90883-9. [DOI] [PubMed] [Google Scholar]
  37. Cooper K. E., Cranston W. I., Honour A. J. Observations on the site & mode of action of pyrogens in the rabbit brain. J Physiol. 1967 Jul;191(2):325–337. doi: 10.1113/jphysiol.1967.sp008253. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Cooper K. E. The neurobiology of fever: thoughts on recent developments. Annu Rev Neurosci. 1987;10:297–324. doi: 10.1146/annurev.ne.10.030187.001501. [DOI] [PubMed] [Google Scholar]
  39. Cornell R. P., Schwartz D. B. Central administration of interleukin 1 elicits hyperinsulinemia in rats. Am J Physiol. 1989 Mar;256(3 Pt 2):R772–R777. doi: 10.1152/ajpregu.1989.256.3.R772. [DOI] [PubMed] [Google Scholar]
  40. Dao T. K., Bell R. C., Feng J., Jameson D. M., Lipton J. M. C-reactive protein, leukocytes, and fever after central IL 1 and alpha-MSH in aged rabbits. Am J Physiol. 1988 Mar;254(3 Pt 2):R401–R409. doi: 10.1152/ajpregu.1988.254.3.R401. [DOI] [PubMed] [Google Scholar]
  41. Davatelis G., Wolpe S. D., Sherry B., Dayer J. M., Chicheportiche R., Cerami A. Macrophage inflammatory protein-1: a prostaglandin-independent endogenous pyrogen. Science. 1989 Feb 24;243(4894 Pt 1):1066–1068. doi: 10.1126/science.2646711. [DOI] [PubMed] [Google Scholar]
  42. Dinarello C. A., Bernheim H. A. Ability of human leukocytic pyrogen to stimulate brain prostaglandin synthesis in vitro. J Neurochem. 1981 Sep;37(3):702–708. doi: 10.1111/j.1471-4159.1982.tb12544.x. [DOI] [PubMed] [Google Scholar]
  43. Dinarello C. A., Bernheim H. A., Duff G. W., Le H. V., Nagabhushan T. L., Hamilton N. C., Coceani F. Mechanisms of fever induced by recombinant human interferon. J Clin Invest. 1984 Sep;74(3):906–913. doi: 10.1172/JCI111508. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Dinarello C. A., Bernheim H. A., Duff G. W., Le H. V., Nagabhushan T. L., Hamilton N. C., Coceani F. Mechanisms of fever induced by recombinant human interferon. J Clin Invest. 1984 Sep;74(3):906–913. doi: 10.1172/JCI111508. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Dinarello C. A., Cannon J. G., Wolff S. M., Bernheim H. A., Beutler B., Cerami A., Figari I. S., Palladino M. A., Jr, O'Connor J. V. Tumor necrosis factor (cachectin) is an endogenous pyrogen and induces production of interleukin 1. J Exp Med. 1986 Jun 1;163(6):1433–1450. doi: 10.1084/jem.163.6.1433. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Dinarello C. A., Cannon J. G., Wolff S. M., Bernheim H. A., Beutler B., Cerami A., Figari I. S., Palladino M. A., Jr, O'Connor J. V. Tumor necrosis factor (cachectin) is an endogenous pyrogen and induces production of interleukin 1. J Exp Med. 1986 Jun 1;163(6):1433–1450. doi: 10.1084/jem.163.6.1433. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Dinarello C. A., Clark B. D., Puren A. J., Savage N., Rosoff P. M. The interleukin 1 receptor. Immunol Today. 1989 Feb;10(2):49–51. doi: 10.1016/0167-5699(89)90304-6. [DOI] [PubMed] [Google Scholar]
  48. Dinarello C. A. Interleukin-1. Rev Infect Dis. 1984 Jan-Feb;6(1):51–95. doi: 10.1093/clinids/6.1.51. [DOI] [PubMed] [Google Scholar]
  49. Farrar W. L., Hill J. M., Harel-Bellan A., Vinocour M. The immune logical brain. Immunol Rev. 1987 Dec;100:361–378. doi: 10.1111/j.1600-065x.1987.tb00539.x. [DOI] [PubMed] [Google Scholar]
  50. Farrar W. L., Kilian P. L., Ruff M. R., Hill J. M., Pert C. B. Visualization and characterization of interleukin 1 receptors in brain. J Immunol. 1987 Jul 15;139(2):459–463. [PubMed] [Google Scholar]
  51. Fong Y., Moldawer L. L., Marano M., Wei H., Barber A., Manogue K., Tracey K. J., Kuo G., Fischman D. A., Cerami A. Cachectin/TNF or IL-1 alpha induces cachexia with redistribution of body proteins. Am J Physiol. 1989 Mar;256(3 Pt 2):R659–R665. doi: 10.1152/ajpregu.1989.256.3.R659. [DOI] [PubMed] [Google Scholar]
  52. Fontana A., Kristensen F., Dubs R., Gemsa D., Weber E. Production of prostaglandin E and an interleukin-1 like factor by cultured astrocytes and C6 glioma cells. J Immunol. 1982 Dec;129(6):2413–2419. [PubMed] [Google Scholar]
  53. Fontana A., Weber E., Dayer J. M. Synthesis of interleukin 1/endogenous pyrogen in the brain of endotoxin-treated mice: a step in fever induction? J Immunol. 1984 Oct;133(4):1696–1698. [PubMed] [Google Scholar]
  54. Giulian D., Baker T. J., Shih L. C., Lachman L. B. Interleukin 1 of the central nervous system is produced by ameboid microglia. J Exp Med. 1986 Aug 1;164(2):594–604. doi: 10.1084/jem.164.2.594. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Helle M., Brakenhoff J. P., De Groot E. R., Aarden L. A. Interleukin 6 is involved in interleukin 1-induced activities. Eur J Immunol. 1988 Jun;18(6):957–959. doi: 10.1002/eji.1830180619. [DOI] [PubMed] [Google Scholar]
  56. Hellon R. F., Townsend Y., Cranston W. I. Naloxone does not influence a pyrogen fever in rabbits. Pflugers Arch. 1985 Jul;404(3):290–291. doi: 10.1007/BF00581254. [DOI] [PubMed] [Google Scholar]
  57. Hori T. Capsaicin and central control of thermoregulation. Pharmacol Ther. 1984;26(3):389–416. doi: 10.1016/0163-7258(84)90041-x. [DOI] [PubMed] [Google Scholar]
  58. Hori T., Kiyohara T., Nakashima T., Shibata M., Koga H. Multimodal responses of preoptic and anterior hypothalamic neurons to thermal and nonthermal homeostatic parameters. Can J Physiol Pharmacol. 1987 Jun;65(6):1290–1298. doi: 10.1139/y87-205. [DOI] [PubMed] [Google Scholar]
  59. Hunter W. S., Blatteis C. M., Llanos-Q J., Mashburn T. A., Jr, Ahokas R. A. Thermal stimulation of the hypothalamus does not evoke the acute-phase reaction. Brain Res Bull. 1987 Jul;19(1):69–74. doi: 10.1016/0361-9230(87)90167-5. [DOI] [PubMed] [Google Scholar]
  60. Kandasamy S. B., Williams B. A. Hyperthermic responses to central injections of some peptide and non-peptide opioids in the guinea-pig. Neuropharmacology. 1983 May;22(5):621–628. doi: 10.1016/0028-3908(83)90154-5. [DOI] [PubMed] [Google Scholar]
  61. Kandasamy S. B., Williams B. A. Peptide and non-peptide opioid-induced hyperthermia in rabbits. Brain Res. 1983 Apr 11;265(1):63–71. doi: 10.1016/0006-8993(83)91334-3. [DOI] [PubMed] [Google Scholar]
  62. Katsuura G., Gottschall P. E., Dahl R. R., Arimura A. Adrenocorticotropin release induced by intracerebroventricular injection of recombinant human interleukin-1 in rats: possible involvement of prostaglandin. Endocrinology. 1988 May;122(5):1773–1779. doi: 10.1210/endo-122-5-1773. [DOI] [PubMed] [Google Scholar]
  63. Krueger J. M., Majde J. A., Blatteis C. M., Endsley J., Ahokas R. A., Cady A. B. Polyriboinosinic:polyribocytidylic acid enhances rabbit slow-wave sleep. Am J Physiol. 1988 Nov;255(5 Pt 2):R748–R755. doi: 10.1152/ajpregu.1988.255.5.R748. [DOI] [PubMed] [Google Scholar]
  64. Kushner I. The phenomenon of the acute phase response. Ann N Y Acad Sci. 1982;389:39–48. doi: 10.1111/j.1749-6632.1982.tb22124.x. [DOI] [PubMed] [Google Scholar]
  65. Larsson I., Landström L. E., Larner E., Lundgren E., Miörner H., Strannegård L. Interferon production in glia and glioma cell lines. Infect Immun. 1978 Dec;22(3):786–789. doi: 10.1128/iai.22.3.786-789.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Le J., Vilcek J. Tumor necrosis factor and interleukin 1: cytokines with multiple overlapping biological activities. Lab Invest. 1987 Mar;56(3):234–248. [PubMed] [Google Scholar]
  67. Mashburn T. A., Jr, Llanos J., Ahokas R. A., Blatteis C. M. Thermal and acute-phase protein responses of guinea pigs to intrapreoptic injections of leukotrienes. Brain Res. 1986 Jun 25;376(2):285–291. doi: 10.1016/0006-8993(86)90191-5. [DOI] [PubMed] [Google Scholar]
  68. McCarthy D. O., Kluger M. J., Vander A. J. Suppression of food intake during infection: is interleukin-1 involved? Am J Clin Nutr. 1985 Dec;42(6):1179–1182. doi: 10.1093/ajcn/42.6.1179. [DOI] [PubMed] [Google Scholar]
  69. Moldawer L. L., Andersson C., Gelin J., Lundholm K. G. Regulation of food intake and hepatic protein synthesis by recombinant-derived cytokines. Am J Physiol. 1988 Mar;254(3 Pt 1):G450–G456. doi: 10.1152/ajpgi.1988.254.3.G450. [DOI] [PubMed] [Google Scholar]
  70. Morimoto A., Murakami N., Watanabe T. Is the central arachidonic acid cascade system involved in the development of acute-phase response in rabbits? J Physiol. 1988 Mar;397:281–289. doi: 10.1113/jphysiol.1988.sp017001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  71. Morimoto A., Sakata Y., Watanabe T., Murakami N. Characteristics of fever and acute-phase response induced in rabbits by IL-1 and TNF. Am J Physiol. 1989 Jan;256(1 Pt 2):R35–R41. doi: 10.1152/ajpregu.1989.256.1.R35. [DOI] [PubMed] [Google Scholar]
  72. Morimoto A., Watanabe T., Sakata Y., Murakami N. Leukocytosis induced by microinjection of endogenous pyrogen or interleukin-1 into the preoptic and anterior hypothalamus. Brain Res. 1988 Dec 20;475(2):345–348. doi: 10.1016/0006-8993(88)90623-3. [DOI] [PubMed] [Google Scholar]
  73. Murakami N., Watanabe T. Activation of ACTH release is mediated by the same molecule as the final mediator, PGE2, of febrile response in rats. Brain Res. 1989 Jan 23;478(1):171–174. doi: 10.1016/0006-8993(89)91492-3. [DOI] [PubMed] [Google Scholar]
  74. Nakashima T., Hori T., Kuriyama K., Matsuda T. Effects of interferon-alpha on the activity of preoptic thermosensitive neurons in tissue slices. Brain Res. 1988 Jun 28;454(1-2):361–367. doi: 10.1016/0006-8993(88)90838-4. [DOI] [PubMed] [Google Scholar]
  75. Nieto-Sampedro M., Berman M. A. Interleukin-1-like activity in rat brain: sources, targets, and effect of injury. J Neurosci Res. 1987;17(3):214–219. doi: 10.1002/jnr.490170303. [DOI] [PubMed] [Google Scholar]
  76. O'Rourke S. T., Rudy T. A. Intracerebroventricular and preoptic injections of leukotrienes C4, D4, and E4 in the rat: lack of febrile effect. Brain Res. 1984 Mar 19;295(2):283–288. doi: 10.1016/0006-8993(84)90977-6. [DOI] [PubMed] [Google Scholar]
  77. Opp M. R., Obál F., Jr, Krueger J. M. Effects of alpha-MSH on sleep, behavior, and brain temperature: interactions with IL 1. Am J Physiol. 1988 Dec;255(6 Pt 2):R914–R922. doi: 10.1152/ajpregu.1988.255.6.R914. [DOI] [PubMed] [Google Scholar]
  78. Perlmutter D. H., Dinarello C. A., Punsal P. I., Colten H. R. Cachectin/tumor necrosis factor regulates hepatic acute-phase gene expression. J Clin Invest. 1986 Nov;78(5):1349–1354. doi: 10.1172/JCI112721. [DOI] [PMC free article] [PubMed] [Google Scholar]
  79. Plata-Salamán C. R. Food intake suppression by growth factors and platelet peptides by direct action in the central nervous system. Neurosci Lett. 1988 Nov 22;94(1-2):161–166. doi: 10.1016/0304-3940(88)90288-1. [DOI] [PubMed] [Google Scholar]
  80. Plata-Salamán C. R., Oomura Y., Kai Y. Tumor necrosis factor and interleukin-1 beta: suppression of food intake by direct action in the central nervous system. Brain Res. 1988 May 10;448(1):106–114. doi: 10.1016/0006-8993(88)91106-7. [DOI] [PubMed] [Google Scholar]
  81. Quan N., Blatteis C. M. Intrapreoptically microdialyzed and microinjected norepinephrine evokes different thermal responses. Am J Physiol. 1989 Oct;257(4 Pt 2):R816–R821. doi: 10.1152/ajpregu.1989.257.4.R816. [DOI] [PubMed] [Google Scholar]
  82. Quan N., Blatteis C. M. Microdialysis: a system for localized drug delivery into the brain. Brain Res Bull. 1989 Apr;22(4):621–625. doi: 10.1016/0361-9230(89)90080-4. [DOI] [PubMed] [Google Scholar]
  83. Ramadori G., Sipe J. D., Dinarello C. A., Mizel S. B., Colten H. R. Pretranslational modulation of acute phase hepatic protein synthesis by murine recombinant interleukin 1 (IL-1) and purified human IL-1. J Exp Med. 1985 Sep 1;162(3):930–942. doi: 10.1084/jem.162.3.930. [DOI] [PMC free article] [PubMed] [Google Scholar]
  84. Rettori V., Jurcovicova J., McCann S. M. Central action of interleukin-1 in altering the release of TSH, growth hormone, and prolactin in the male rat. J Neurosci Res. 1987;18(1):179–183. doi: 10.1002/jnr.490180125. [DOI] [PubMed] [Google Scholar]
  85. Rosendorff C., Mooney J. J. Central nervous system sites of action of a purified leucocyte pyrogen. Am J Physiol. 1971 Mar;220(3):597–603. doi: 10.1152/ajplegacy.1971.220.3.597. [DOI] [PubMed] [Google Scholar]
  86. Rotondo D., Abul H. T., Milton A. S., Davidson J. Pyrogenic immunomodulators increase the level of prostaglandin E2 in the blood simultaneously with the onset of fever. Eur J Pharmacol. 1988 Sep 13;154(2):145–152. doi: 10.1016/0014-2999(88)90091-x. [DOI] [PubMed] [Google Scholar]
  87. Sakaguchi S., Glotzbach S. F., Heller H. C. Influence of hypothalamic and ambient temperatures on sleep in kangaroo rats. Am J Physiol. 1979 Jul;237(1):R80–R88. doi: 10.1152/ajpregu.1979.237.1.R80. [DOI] [PubMed] [Google Scholar]
  88. Sakata Y. Effects of pyrogen on the medullary temperature-responsive neurone of rabbits. Jpn J Physiol. 1979;29(5):585–596. doi: 10.2170/jjphysiol.29.585. [DOI] [PubMed] [Google Scholar]
  89. Sakata Y., Morimoto A., Takase Y., Murakami N. Direct effects of endogenous pyrogen on medullary temperature-responsive neurons in rabbits. Jpn J Physiol. 1981;31(2):247–257. doi: 10.2170/jjphysiol.31.247. [DOI] [PubMed] [Google Scholar]
  90. Sapolsky R., Rivier C., Yamamoto G., Plotsky P., Vale W. Interleukin-1 stimulates the secretion of hypothalamic corticotropin-releasing factor. Science. 1987 Oct 23;238(4826):522–524. doi: 10.1126/science.2821621. [DOI] [PubMed] [Google Scholar]
  91. Scott I. M., Fertel R. H., Boulant J. A. Leukocytic pyrogen effects on prostaglandins in hypothalamic tissue slices. Am J Physiol. 1987 Jul;253(1 Pt 2):R71–R76. doi: 10.1152/ajpregu.1987.253.1.R71. [DOI] [PubMed] [Google Scholar]
  92. Shoham S., Blatteis C. M., Krueger J. M. Effects of preoptic area lesions on muramyl dipeptide-induced sleep and fever. Brain Res. 1989 Jan 9;476(2):396–399. doi: 10.1016/0006-8993(89)91267-5. [DOI] [PubMed] [Google Scholar]
  93. Sirko S., Bishai I., Coceani F. Prostaglandin formation in the hypothalamus in vivo: effect of pyrogens. Am J Physiol. 1989 Mar;256(3 Pt 2):R616–R624. doi: 10.1152/ajpregu.1989.256.3.R616. [DOI] [PubMed] [Google Scholar]
  94. Sobrado J., Moldawer L. L., Bistrian B. R., Dinarello C. A., Blackburn G. L. Effect of ibuprofen on fever and metabolic changes induced by continuous infusion of leukocytic pyrogen (interleukin 1) or endotoxin. Infect Immun. 1983 Dec;42(3):997–1005. doi: 10.1128/iai.42.3.997-1005.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  95. Stitt J. T. Evidence for the involvement of the organum vasculosum laminae terminalis in the febrile response of rabbits and rats. J Physiol. 1985 Nov;368:501–511. doi: 10.1113/jphysiol.1985.sp015872. [DOI] [PMC free article] [PubMed] [Google Scholar]
  96. Stitt J. T., Hardy J. D. Microelectrophoresis of PGE1 onto single units in the rabbit hypothalamus. Am J Physiol. 1975 Jul;229(1):240–245. doi: 10.1152/ajplegacy.1975.229.1.240. [DOI] [PubMed] [Google Scholar]
  97. Stitt J. T. Prostaglandin E as the neural mediator of the febrile response. Yale J Biol Med. 1986 Mar-Apr;59(2):137–149. [PMC free article] [PubMed] [Google Scholar]
  98. Tocco R. J., Kahn L. L., Kluger M. J., Vander A. J. Relationship of trace metals to fever during infection: are prostaglandins involved? Am J Physiol. 1983 Mar;244(3):R368–R373. doi: 10.1152/ajpregu.1983.244.3.R368. [DOI] [PubMed] [Google Scholar]
  99. Turchik J. B., Bornstein D. L. Role of the central nervous system in acute-phase responses to leukocytic pyrogen. Infect Immun. 1980 Nov;30(2):439–444. doi: 10.1128/iai.30.2.439-444.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  100. Watanabe T., Morimoto A., Murakami N. Effect of PGE2 on preoptic and anterior hypothalamic neurons using brain slice preparation. J Appl Physiol (1985) 1987 Sep;63(3):918–922. doi: 10.1152/jappl.1987.63.3.918. [DOI] [PubMed] [Google Scholar]
  101. Weigent D. A., Blalock J. E. Interactions between the neuroendocrine and immune systems: common hormones and receptors. Immunol Rev. 1987 Dec;100:79–108. doi: 10.1111/j.1600-065x.1987.tb00528.x. [DOI] [PubMed] [Google Scholar]
  102. Zawalich W. S., Zawalich K. C. Interleukin 1 is a potent stimulator of islet insulin secretion and phosphoinositide hydrolysis. Am J Physiol. 1989 Jan;256(1 Pt 1):E19–E24. doi: 10.1152/ajpendo.1989.256.1.E19. [DOI] [PubMed] [Google Scholar]
  103. del Rey A., Besedovsky H. Interleukin 1 affects glucose homeostasis. Am J Physiol. 1987 Nov;253(5 Pt 2):R794–R798. doi: 10.1152/ajpregu.1987.253.5.R794. [DOI] [PubMed] [Google Scholar]

Articles from The Yale Journal of Biology and Medicine are provided here courtesy of Yale Journal of Biology and Medicine

RESOURCES