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. 1992 Mar;448:307–320. doi: 10.1113/jphysiol.1992.sp019043

Cardiovascular responses induced in free-moving rats by immune cytokines.

K Morimoto 1, A Morimoto 1, T Nakamori 1, N Tan 1, T Minagawa 1, N Murakami 1
PMCID: PMC1176201  PMID: 1593469

Abstract

1. We investigated the effect of intraperitoneal (I.P.) injections of the immune cytokines, interleukin-1 beta (IL-1 beta) and tumour necrosis factor (TNF) on cardiovascular responses in free-moving rats, using a biotelemetry system. 2. The I.P. injection of a small dose of IL-1 beta (1 microgram/kg) induced a monophasic increase in the heart rate, and that of a large dose (10 micrograms/kg) induced biphasic increases in the blood pressure and heart rate. However, the I.P. injection of any of several doses of TNF (1, 10 and 50 micrograms/kg) had no effect on cardiovascular responses in rats. 3. Pre-treatment with I.P. injection of indomethacin (10 mg/kg), an inhibitor of cyclo-oxygenase, significantly suppressed the cardiovascular responses and the increase in the plasma noradrenaline (NA) concentration induced by I.P. injection of IL-1 beta. 4. Microinjection of IL-1 beta (1 and 10 ng) into the preoptic and anterior hypothalamic (PO-AH) region induced dose-dependent increases in the blood pressure and heart rate in rats. These responses were also suppressed by pretreatment with I.P. indomethacin (10 mg/kg). In addition, microinjection of prostaglandin E2 (20 and 100 ng) into the PO-AH region increased blood pressure and heart rate, but that of prostaglandin D2 (100 ng) had no effect. 5. The present results suggest that IL-1 beta stimulates the release of prostaglandins, presumably E series, near regions of the hypothalamus, which act on the hypothalamus to induce activation of the sympathetic nervous system. Subsequently, the blood pressure, heart rate and the plasma level of NA increase.

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Selected References

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  1. Beasley D., Cohen R. A., Levinsky N. G. Interleukin 1 inhibits contraction of vascular smooth muscle. J Clin Invest. 1989 Jan;83(1):331–335. doi: 10.1172/JCI113879. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bernheim H. A., Gilbert T. M., Stitt J. T. Prostaglandin E levels in third ventricular cerebrospinal fluid of rabbits during fever and changes in body temperature. J Physiol. 1980 Apr;301:69–78. doi: 10.1113/jphysiol.1980.sp013189. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. 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]
  4. Breuhaus B. A., Demarest K. T., Chimoskey J. E. Comparison of intracerebroventricular and intracarotid infusions of PGE2 in conscious sheep. Am J Physiol. 1989 Mar;256(3 Pt 2):R685–R693. doi: 10.1152/ajpregu.1989.256.3.R685. [DOI] [PubMed] [Google Scholar]
  5. 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]
  6. Eguchi N., Hayashi H., Urade Y., Ito S., Hayaishi O. Central action of prostaglandin E2 and its methyl ester in the induction of hyperthermia after their systemic administration in urethane-anesthetized rats. J Pharmacol Exp Ther. 1988 Nov;247(2):671–679. [PubMed] [Google Scholar]
  7. 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]
  8. Feuerstein G., Adelberg S. A., Kopin I. J., Jacobowitz D. M. Hypothalamic sites for cardiovascular and sympathetic modulation by prostaglandin E2. Brain Res. 1982 Jan 14;231(2):335–342. doi: 10.1016/0006-8993(82)90370-5. [DOI] [PubMed] [Google Scholar]
  9. Kasting N. W., Martin J. B. Altered release of growth hormone and thyrotropin induced by endotoxin in the rat. Am J Physiol. 1982 Oct;243(4):E332–E337. doi: 10.1152/ajpendo.1982.243.4.E332. [DOI] [PubMed] [Google Scholar]
  10. Kluger M. J., Ringler D. H., Anver M. R. Fever and survival. Science. 1975 Apr 11;188(4184):166–168. [PubMed] [Google Scholar]
  11. Kluger M. J., Rothenburg B. A. Fever and reduced iron: their interaction as a host defense response to bacterial infection. Science. 1979 Jan 26;203(4378):374–376. doi: 10.1126/science.760197. [DOI] [PubMed] [Google Scholar]
  12. Malkinson T. J., Cooper K. E., Veale W. L. Cerebrospinal fluid pressure in conscious rats during prostaglandin E1 fever. Am J Physiol. 1990 Mar;258(3 Pt 2):R783–R787. doi: 10.1152/ajpregu.1990.258.3.R783. [DOI] [PubMed] [Google Scholar]
  13. Mathison J. C., Wolfson E., Ulevitch R. J. Participation of tumor necrosis factor in the mediation of gram negative bacterial lipopolysaccharide-induced injury in rabbits. J Clin Invest. 1988 Jun;81(6):1925–1937. doi: 10.1172/JCI113540. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Matsumura K., Watanabe Y., Onoe H., Watanabe Y., Hayaishi O. High density of prostaglandin E2 binding sites in the anterior wall of the 3rd ventricle: a possible site of its hyperthermic action. Brain Res. 1990 Nov 12;533(1):147–151. doi: 10.1016/0006-8993(90)91808-t. [DOI] [PubMed] [Google Scholar]
  15. Morimoto A., Murakami N., Nakamori T., Sakata Y., Watanabe T. Brain regions involved in the development of acute phase responses accompanying fever in rabbits. J Physiol. 1989 Sep;416:645–657. doi: 10.1113/jphysiol.1989.sp017782. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Morimoto A., Murakami N., Nakamori T., Sakata Y., Watanabe T. Possible involvement of prostaglandin E in development of ACTH response in rats induced by human recombinant interleukin-1. J Physiol. 1989 Apr;411:245–256. doi: 10.1113/jphysiol.1989.sp017571. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Morimoto A., Murakami N., Nakamori T., Watanabe T. Evidence for separate mechanisms of induction of biphasic fever inside and outside the blood-brain barrier in rabbits. J Physiol. 1987 Feb;383:629–637. doi: 10.1113/jphysiol.1987.sp016433. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Morimoto A., Watanabe T., Ono T., Sakata Y., Murakami N. Rat endogenous pyrogen and fever. Am J Physiol. 1986 May;250(5 Pt 2):R776–R782. doi: 10.1152/ajpregu.1986.250.5.R776. [DOI] [PubMed] [Google Scholar]
  19. Piper P. J., Vane J. R., Wyllie J. H. Inactivation of prostaglandins by the lungs. Nature. 1970 Feb 14;225(5233):600–604. doi: 10.1038/225600a0. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. Shido O., Nagasaka T. Cardiovascular and thermal responses to intravenous endotoxin in guinea pigs. Jpn J Physiol. 1986;36(3):543–554. doi: 10.2170/jjphysiol.36.543. [DOI] [PubMed] [Google Scholar]
  22. Skarnes R. C., Brown S. K., Hull S. S., McCracken J. A. Role of prostaglandin E in the biphasic fever response to endotoxin. J Exp Med. 1981 Oct 1;154(4):1212–1224. doi: 10.1084/jem.154.4.1212. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Stitt J. T. Prosaglandin E1 fever induced in rabbits. J Physiol. 1973 Jul;232(1):163–179. doi: 10.1113/jphysiol.1973.sp010262. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Weinberg J. R., Wright D. J., Guz A. Interleukin-1 and tumour necrosis factor cause hypotension in the conscious rabbit. Clin Sci (Lond) 1988 Sep;75(3):251–255. doi: 10.1042/cs0750251. [DOI] [PubMed] [Google Scholar]
  25. Yoshizumi M., Kurihara H., Morita T., Yamashita T., Oh-hashi Y., Sugiyama T., Takaku F., Yanagisawa M., Masaki T., Yazaki Y. Interleukin 1 increases the production of endothelin-1 by cultured endothelial cells. Biochem Biophys Res Commun. 1990 Jan 15;166(1):324–329. doi: 10.1016/0006-291x(90)91948-r. [DOI] [PubMed] [Google Scholar]

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