Skip to main content
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1993 May;109(1):88–93. doi: 10.1111/j.1476-5381.1993.tb13535.x

Effects of pyrogenic immunomodulators on the release of corticotrophin-releasing factor-41 and prostaglandin E2 from the intact rat hypothalamus in vitro.

N G Milton 1, C H Self 1, E W Hillhouse 1
PMCID: PMC2175569  PMID: 8495249

Abstract

1. The actions of the following pyrogens: lipopolysaccharide (LPS), polyinosinic:polycytidylic acid (Poly-I:C), human interleukin (IL)-1 alpha and IL-1 beta, human IL-6 and rat interferon (INF) on corticotrophin-releasing factor-41 (CRF-41) and prostaglandin E2 (PGE2) release from the intact rat hypothalamus in vitro have been studied. 2. Rat hypothalami were incubated in vitro in an artificial cerebrospinal fluid. Immunoreactive (ir)-CFR-41 and PGE2 released into the medium were measured by two-site enzyme amplified immunometric assay (EAIA) and radioimmunoassay (RIA) respectively. 3. Human IL-6 (1 to 10,000 IU ml-1) caused a dose-dependent release of irCRF-41, rising to a maximal 3-4 fold increase over basal at the highest dose tested. Human IL-1 alpha (1 to 1000 IU ml-1), human IL-1 beta (1 to 1000 IU ml-1), poly-I:C (10 pg ml-1 to 100 micrograms ml-1) and rat INF (1 to 10,000 IRu ml-1) all failed to alter irCRF-41 release. 4. LPS (1 mg ml-1) caused a 35% decrease in irCRF-41 release; however, over the dose-range of 0.1 microgram ml-1 to 100 micrograms ml-1, LPS failed to alter irCRF-41 release. The decreased irCRF-41 release in response to LPS (1 mg ml-1) was accompanied by a decrease in the subsequent 56 mM KCl stimulation of irCRF-41. 5. Human IL-1 alpha and IL-1 beta (1000 IU ml-1) were able to stimulate the release of irPGE2 from intact hypothalami, causing a 2 fold increase over basal release.(ABSTRACT TRUNCATED AT 250 WORDS)

Full text

PDF
88

Selected References

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

  1. Bernardini R., Chiarenza A., Calogero A. E., Gold P. W., Chrousos G. P. Arachidonic acid metabolites modulate rat hypothalamic corticotropin-releasing hormone secretion in vitro. Neuroendocrinology. 1989 Dec;50(6):708–715. doi: 10.1159/000125303. [DOI] [PubMed] [Google Scholar]
  2. Bradbury M. W., Burden J., Hillhouse E. W., Jones M. T. Stimulation electrically and by acetylcholine of the rat hypothalamus in vitro. J Physiol. 1974 Jun;239(2):269–283. doi: 10.1113/jphysiol.1974.sp010568. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. 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]
  4. 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]
  5. Feldberg W., Gupta K. P., Milton A. S., Wendlandt S. Effect of pyrogen and antipyretics on prostaglandin acitvity in cisternal c.s.f. of unanaesthetized cats. J Physiol. 1973 Oct;234(2):279–303. doi: 10.1113/jphysiol.1973.sp010346. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Feldberg W., Gupta K. P. Pyrogen fever and prostaglandin-like activity in cerebrospinal fluid. J Physiol. 1973 Jan;228(1):41–53. doi: 10.1113/jphysiol.1973.sp010071. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Gwosdow A. R., Kumar M. S., Bode H. H. Interleukin 1 stimulation of the hypothalamic-pituitary-adrenal axis. Am J Physiol. 1990 Jan;258(1 Pt 1):E65–E70. doi: 10.1152/ajpendo.1990.258.1.E65. [DOI] [PubMed] [Google Scholar]
  8. Hillhouse E. W., Milton N. G. Effect of acetylcholine and 5-hydroxytryptamine on the secretion of corticotrophin-releasing factor-41 and arginine vasopressin from the rat hypothalamus in vitro. J Endocrinol. 1989 Sep;122(3):713–718. doi: 10.1677/joe.0.1220713. [DOI] [PubMed] [Google Scholar]
  9. Hillhouse E. W., Milton N. G. Effect of noradrenaline and gamma-aminobutyric acid on the secretion of corticotrophin-releasing factor-41 and arginine vasopressin from the rat hypothalamus in vitro. J Endocrinol. 1989 Sep;122(3):719–723. doi: 10.1677/joe.0.1220719. [DOI] [PubMed] [Google Scholar]
  10. Katsuura G., Arimura A., Koves K., Gottschall P. E. Involvement of organum vasculosum of lamina terminalis and preoptic area in interleukin 1 beta-induced ACTH release. Am J Physiol. 1990 Jan;258(1 Pt 1):E163–E171. doi: 10.1152/ajpendo.1990.258.1.E163. [DOI] [PubMed] [Google Scholar]
  11. Milton A. S., Wendlandt S. Effects on body temperature of prostaglandins of the A, E and F series on injection into the third ventricle of unanaesthetized cats and rabbits. J Physiol. 1971 Oct;218(2):325–336. doi: 10.1113/jphysiol.1971.sp009620. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Milton N. G., Hillhouse E. W., Milton A. S. Activation of the hypothalamo-pituitary-adrenocortical axis in the conscious rabbit by the pyrogen polyinosinic:polycytidylic acid is dependent on corticotrophin-releasing factor-41. J Endocrinol. 1992 Oct;135(1):69–75. doi: 10.1677/joe.0.1350069. [DOI] [PubMed] [Google Scholar]
  13. Milton N. G., Hillhouse E. W., Nicholson S. A., Self C. H., McGregor A. M. Production and utilization of monoclonal antibodies to human/rat corticotrophin-releasing factor-41. J Mol Endocrinol. 1990 Oct;5(2):159–166. doi: 10.1677/jme.0.0050159. [DOI] [PubMed] [Google Scholar]
  14. Naitoh Y., Fukata J., Tominaga T., Nakai Y., Tamai S., Mori K., Imura H. Interleukin-6 stimulates the secretion of adrenocorticotropic hormone in conscious, freely-moving rats. Biochem Biophys Res Commun. 1988 Sep 30;155(3):1459–1463. doi: 10.1016/s0006-291x(88)81305-6. [DOI] [PubMed] [Google Scholar]
  15. Navarra P., Tsagarakis S., Faria M. S., Rees L. H., Besser G. M., Grossman A. B. Interleukins-1 and -6 stimulate the release of corticotropin-releasing hormone-41 from rat hypothalamus in vitro via the eicosanoid cyclooxygenase pathway. Endocrinology. 1991 Jan;128(1):37–44. doi: 10.1210/endo-128-1-37. [DOI] [PubMed] [Google Scholar]
  16. Palkovits M., Brownstein M. J., Vale W. Distribution of corticotropin-releasing factor in rat brain. Fed Proc. 1985 Jan;44(1 Pt 2):215–219. [PubMed] [Google Scholar]
  17. Petrusz P., Merchenthaler I., Maderdrut J. L., Heitz P. U. Central and peripheral distribution of corticotropin-releasing factor. Fed Proc. 1985 Jan;44(1 Pt 2):229–235. [PubMed] [Google Scholar]
  18. Rivier C., Vale W. Stimulatory effect of interleukin-1 on adrenocorticotropin secretion in the rat: is it modulated by prostaglandins? Endocrinology. 1991 Jul;129(1):384–388. doi: 10.1210/endo-129-1-384. [DOI] [PubMed] [Google Scholar]
  19. 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]
  20. 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]
  21. Sawchenko P. E., Swanson L. W. Localization, colocalization, and plasticity of corticotropin-releasing factor immunoreactivity in rat brain. Fed Proc. 1985 Jan;44(1 Pt 2):221–227. [PubMed] [Google Scholar]
  22. Souvannavong V., Adam A. Macrophages from C3H/HeJ mice require an additional step to produce monokines: synergistic effects of silica and poly(I:C) in the release of interleukin 1. J Leukoc Biol. 1990 Aug;48(2):183–192. doi: 10.1002/jlb.48.2.183. [DOI] [PubMed] [Google Scholar]
  23. Tsagarakis S., Gillies G., Rees L. H., Besser M., Grossman A. Interleukin-1 directly stimulates the release of corticotrophin releasing factor from rat hypothalamus. Neuroendocrinology. 1989 Jan;49(1):98–101. doi: 10.1159/000125096. [DOI] [PubMed] [Google Scholar]
  24. Tsagarakis S., Holly J. M., Rees L. H., Besser G. M., Grossman A. Acetylcholine and norepinephrine stimulate the release of corticotropin-releasing factor-41 from the rat hypothalamus in vitro. Endocrinology. 1988 Oct;123(4):1962–1969. doi: 10.1210/endo-123-4-1962. [DOI] [PubMed] [Google Scholar]
  25. Uehara A., Gottschall P. E., Dahl R. R., Arimura A. Interleukin-1 stimulates ACTH release by an indirect action which requires endogenous corticotropin releasing factor. Endocrinology. 1987 Oct;121(4):1580–1582. doi: 10.1210/endo-121-4-1580. [DOI] [PubMed] [Google Scholar]
  26. Woloski B. M., Smith E. M., Meyer W. J., 3rd, Fuller G. M., Blalock J. E. Corticotropin-releasing activity of monokines. Science. 1985 Nov 29;230(4729):1035–1037. doi: 10.1126/science.2997929. [DOI] [PubMed] [Google Scholar]
  27. Yasuda N., Greer M. A. Evidence that the hypothalamus mediates endotoxin stimulation of adrenocorticotropic hormone secretion. Endocrinology. 1978 Mar;102(3):947–953. doi: 10.1210/endo-102-3-947. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES