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. 1967 Jul;191(2):325–337. doi: 10.1113/jphysiol.1967.sp008253

Observations on the site and mode of action of pyrogens in the rabbit brain

K E Cooper, W I Cranston, A J Honour
PMCID: PMC1365456  PMID: 6050108

Abstract

1. Leucocyte pyrogen has been injected bilaterally into various parts of the rabbit brain. It caused fever when injected into the pre-optic area and the anterior hypothalamus, but not when injected into the posterior hypothalamus, the mid-brain, the pons, the cerebellum or the cerebral cortex.

2. The mean time which elapsed between a leucocyte pyrogen injection into the anterior hypothalamus and the onset of fever was 7·8 min. For similar injections of bacterial pyrogen the time lag was 24·8 min. The mean time lag between bilateral injections of noradrenaline into the anterior hypothalamus and the onset of fever was 7·4 min.

3. The amount of leucocyte pyrogen required to cause fever when injected into the anterior hypothalamus was less than 1/100 of that required to cause a similar fever on intravenous injection. The quantity of bacterial pyrogen injected into the hypothalamus was of the same order as that which would cause a similar fever on intravenous injection.

4. Control injections of saline, plasma, cerebrospinal fluid, heated leucocyte pyrogen and red cells into the anterior hypothalamus did not cause fever.

5. After attempts to deplete the hypothalamus of its monoamine stores by intraventricular injections of reserpine, the rabbit had fever as a result of an intravenous injection of bacterial pyrogen.

6. We conclude that the anterior hypothalamus and the pre-optic area are sites at which leucocyte pyrogen acts to cause fever in the rabbit. The mechanism of this febrile response is not clear, but it appears that part, at least, of the response could be mediated by a mechanism other than release of noradrenaline or failure to release 5-HT.

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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. Andersson B., Jobin M., Olsson K. Serotonine and temperature control. Acta Physiol Scand. 1966 May;67(1):50–56. doi: 10.1111/j.1748-1716.1966.tb03286.x. [DOI] [PubMed] [Google Scholar]
  3. BENNETT I. L., Jr, BEESON P. B. Studies on the pathogenesis of fever. II. Characterization of fever-producing substances from polymorphonuclear leukocytes and from the fluid of sterile exudates. J Exp Med. 1953 Nov;98(5):493–508. doi: 10.1084/jem.98.5.493. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. BENNETT I. L., Jr, PETERSDORF R. G., KEENE W. R. Pathogenesis of fever: evidence for direct cerebral action of bacterial endotoxins. Trans Assoc Am Physicians. 1957;70:64–73. [PubMed] [Google Scholar]
  5. Bligh J. The thermosensitivity of the hypothalamus and thermoregulation in mammals. Biol Rev Camb Philos Soc. 1966 Aug;41(3):317–368. doi: 10.1111/j.1469-185x.1966.tb01496.x. [DOI] [PubMed] [Google Scholar]
  6. CHAMBERS W. W., KOENIG H. Site of action in the central nervous system of a bacterial pyrogen. Am J Physiol. 1949 Nov;159(2):209–216. doi: 10.1152/ajplegacy.1949.159.2.209. [DOI] [PubMed] [Google Scholar]
  7. Cooper K. E., Cranston W. I., Honour A. J. Effects of intraventricular and intrahypothalamic injection of noradrenaline and 5-HT on body temperature in conscious rabbits. J Physiol. 1965 Dec;181(4):852–864. doi: 10.1113/jphysiol.1965.sp007801. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cooper K. E. The role of the hypothalamus in the genesis of fever. Proc R Soc Med. 1965 Sep;58(9):740–740. doi: 10.1177/003591576505800941. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. FELDBERG W., MYERS R. D. A NEW CONCEPT OF TEMPERATURE REGULATION BY AMINES IN THE HYPOTHALAMUS. Nature. 1963 Dec 28;200:1325–1325. doi: 10.1038/2001325a0. [DOI] [PubMed] [Google Scholar]
  10. FELDBERG W., MYERS R. D. CHANGES IN TEMPERATURE PRODUCED BY MICRO-INJECTIONS OF AMINES INTO THE ANTERIOR HYPOTHALAMUS OF CATS. J Physiol. 1965 Mar;177:239–245. doi: 10.1113/jphysiol.1965.sp007589. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. FESSLER J. H., COOPER K. E., CRANSTON W. I., VOLLUM R. L. Observations on the production of pyrogenic substances by rabbit and human leucocytes. J Exp Med. 1961 Jun 1;113:1127–1140. doi: 10.1084/jem.113.6.1127. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Findlay J. D., Robertshaw D. The mechanism of body temperature changes induced by intraventricular injections of adrenaline, noradrenaline and 5-hydroxytryptamine in the ox (Bos taurus). J Physiol. 1967 Apr;189(2):329–336. doi: 10.1113/jphysiol.1967.sp008171. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. HARDY J. D., HELLON R. F., SUTHERLAND K. TEMPERATURE-SENSITIVE NEURONES IN THE DOG'S HYPOTHALAMUS. J Physiol. 1964 Dec;175:242–253. doi: 10.1113/jphysiol.1964.sp007515. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. KING M. K., WOOD W. B., Jr Studies on the pathogenesis of fever. IV. The site of action of leucocytic and circulating endogenous pyrogen. J Exp Med. 1958 Feb 1;107(2):291–303. doi: 10.1084/jem.107.2.291. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Rafter G. W., Cheuk S. F., Krause D. W., Wood W. B., Jr Studies on the pathogenesis of fever. XIV. Further observations on the chemistry of leukocytic pyrogen. J Exp Med. 1966 Mar 1;123(3):433–444. doi: 10.1084/jem.123.3.433. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. VILLABLANCA J., MYERS R. D. FEVER PRODUCED BY MICROINJECTION OF TYPHOID VACCINE INTO HYPOTHALAMUS OF CATS. Am J Physiol. 1965 Apr;208:703–707. doi: 10.1152/ajplegacy.1965.208.4.703. [DOI] [PubMed] [Google Scholar]

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