Abstract
Three exogenous pyrogens (Escherichia coli lipopolysaccharide, synthetic double-stranded ribonucleic acid. Newcastle disease virus) were compared with respect to their mechanisms of fever induction in rabbits. All inducers stimulated the production of an endogenous pyrogen demonstrated in the blood as well as prostaglandins of the E group, and of cyclic adenosine 3',5'-monophosphate in the cerebrospinal fluid. The concentrations of these compounds were elevated approximately twofold as compared to the controls. Independently of the mode of induction, the fever reaction could be prevented by pretreatment with 5 mg of cycloheximide per kg, although the three fever mediators were induced as in febrile animals. Consequently, at least one additional fever mediator that is sensitive to a 30 to 50% inhibition of protein synthesis by cycloheximide has to be postulated. The comparable reactions of the rabbits after administration of different pyrogens argues for a similar fever mechanism. In contrast to fever induction there was no stimulation of endogenous pyrogen, prostaglandins of the E group, and cyclic adenosine 3',5'-monophosphate in hyperthermia as a consequence of exposure of the animals to exogenous overheating. Furthermore, hyperthermia could not be prevented by cycloheximide.
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- ADLER R. D., JOY R. J. FEBRILE RESPONSES TO THE INTRACISTERNAL INJECTION OF ENDOGENOUS (LEUCOCYTIC) PYROGEN IN THE RABBIT. Proc Soc Exp Biol Med. 1965 Jul;119:660–663. doi: 10.3181/00379727-119-30264. [DOI] [PubMed] [Google Scholar]
- ATKINS E., CRONIN M., ISACSON P. ENDOGENOUS PYROGEN RELEASE FROM RABBIT BLOOD CELLS INCUBATED IN VITRO WITH PARAINFLUENZA VIRUS. Science. 1964 Dec 11;146(3650):1469–1470. doi: 10.1126/science.146.3650.1469. [DOI] [PubMed] [Google Scholar]
- ATKINS E., HUANG W. C. Studies on the pathogenesis of fever with influenzal viruses. I. The appearance of an endogenous pyrogen in the blood following intravenous injection of virus. J Exp Med. 1958 Mar 1;107(3):383–401. doi: 10.1084/jem.107.3.383. [DOI] [PMC free article] [PubMed] [Google Scholar]
- ATKINS E. Pathogenesis of fever. Physiol Rev. 1960 Jul;40:580–646. doi: 10.1152/physrev.1960.40.3.580. [DOI] [PubMed] [Google Scholar]
- ATKINS E., WOOD W. B., Jr Studies on the pathogenesis of fever. I. The presence of transferable pyrogen in the blood stream following the injection of typhoid vaccine. J Exp Med. 1955 May 1;101(5):519–528. doi: 10.1084/jem.101.5.519. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Absher M., Stinebring W. R. Toxic properties of a synthetic double-stranded RNA. Endotoxin-like properties of poly I. poly C, an interferon stimulator. Nature. 1969 Aug 16;223(5207):715–717. doi: 10.1038/223715a0. [DOI] [PubMed] [Google Scholar]
- BORNSTEIN D. L., BREDENBERG C., WOOD W. B., Jr Studies on the pathogenesis of fever. XI. Quantitative features of the febrile response to leucocytic pyrogen. J Exp Med. 1963 Mar 1;117:349–364. doi: 10.1084/jem.117.3.349. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Clark W. G., Cumby H. R., Davis N. E., 4th The hyperthermic effect of intracerebroventricular cholera enterotoxin in the unanaesthetized cat. J Physiol. 1974 Jul;240(2):493–504. doi: 10.1113/jphysiol.1974.sp010619. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Collier H. O., Roy A. C. Morphine-like drugs inhibit the stimulation of E prostaglandins of cyclic AMP formation by rat brain homogenate. Nature. 1974 Mar 1;248(5443):24–27. doi: 10.1038/248024a0. [DOI] [PubMed] [Google Scholar]
- Cox C. G., Rafter G. W. Pyrogen and enzyme release from rabbit blood leukocytes promoted by endotoxin and polyinosinic polycytidylic acid. Biochem Med. 1971 Jun;5(3):227–236. doi: 10.1016/0006-2944(71)90025-1. [DOI] [PubMed] [Google Scholar]
- 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]
- Fleetwood M. K., Gander G. W., Goodale F. Effect of metabolic inhibitors on pyrogen production by rabbit leukocytes. Proc Soc Exp Biol Med. 1975 Jun;149(2):336–339. doi: 10.3181/00379727-149-38802. [DOI] [PubMed] [Google Scholar]
- Florendo N. T., Barrnett R. J., Greengard P. Cyclic 3',5'-nucleotide phosphodiesterase: cytochemical localization in cerebral cortex. Science. 1971 Aug 20;173(3998):745–747. doi: 10.1126/science.173.3998.745. [DOI] [PubMed] [Google Scholar]
- GILLMAN S. M., BORNSTEIN D. L., WOOD W. B., Jr Studies on the pathogenesis of fever. VIII. Further observations on the role of endogenous pyrogen in endotoxin fever. J Exp Med. 1961 Nov 1;114:729–739. doi: 10.1084/jem.114.5.729. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gessa G. L., Krishna G., Forn J., Tagliamonte A., Brodie B. B. Behavioral and vegetative effects produced by dibutyryl cyclic AMP injected into different areas of the brain. Adv Biochem Psychopharmacol. 1970;3:371–381. [PubMed] [Google Scholar]
- Gilman A. G. A protein binding assay for adenosine 3':5'-cyclic monophosphate. Proc Natl Acad Sci U S A. 1970 Sep;67(1):305–312. doi: 10.1073/pnas.67.1.305. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gilman A. G., Nirenberg M. Regulation of adenosine 3',5'-cyclic monophosphate metabolism in cultured neuroblastoma cells. Nature. 1971 Dec 10;234(5328):356–358. doi: 10.1038/234356a0. [DOI] [PubMed] [Google Scholar]
- Gilman A. G. Regulation of cyclic AMP metabolism in cultured cells of the nervous system. Adv Cyclic Nucleotide Res. 1972;1:389–410. [PubMed] [Google Scholar]
- Grahame-Smith D. G. The prevention by inhibitors of brain proptein synthesis of the hyperactivity and hyperpyrexia produced in rats by monoamine oxidase inhibition and the administration of L-tryptophan or 5-methoxy-N,N-dimethyltryptamine. J Neurochem. 1972 Oct;19(10):2409–2422. doi: 10.1111/j.1471-4159.1972.tb01295.x. [DOI] [PubMed] [Google Scholar]
- Hahn H. H., Char D. C., Postel W. B., Wood W. B., Jr Studies on the pathogenesis of fever. XV. The production of endogenous pyrogen by peritoneal macrophages. J Exp Med. 1967 Aug 1;126(2):385–394. doi: 10.1084/jem.126.2.385. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jaffe B. M., Behrman H. R., Parker C. W. Radioimmunoassay measurement of prostaglandins E, A, and F in human plasma. J Clin Invest. 1973 Feb;52(2):398–405. doi: 10.1172/JCI107196. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Kozak M. S., Hahn H. H., Lennarz W. J., Wood W. B., Jr Studies on the pathogenesis of fever. XVI. Purification and further chemical characterization of granulocytic pyrogen. J Exp Med. 1968 Feb 1;127(2):341–357. doi: 10.1084/jem.127.2.341. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lau R. Y., Van Alstyne D., Berckmans R., Graham A. F. Synthesis of reovirus-specific polypeptides in cells pretreated with cycloheximide. J Virol. 1975 Sep;16(3):470–478. doi: 10.1128/jvi.16.3.470-478.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lindsay H. L., Trown P. W., Brandt J., Forbes M. Pyrogenicity of poly I. poly C in rabbits. Nature. 1969 Aug 16;223(5207):717–718. doi: 10.1038/223717a0. [DOI] [PubMed] [Google Scholar]
- Moore D. M., Murphy P. A., Chesney P. J., Wood W. B., Jr Synthesis of endogenous pyrogen by rabbit leukocytes. J Exp Med. 1973 May 1;137(5):1263–1274. doi: 10.1084/jem.137.5.1263. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Orczyk G. P., Behrman H. R. Ovulation blockade by aspirin or indomethacin--in vivo evidence for a role of prostaglandin in gonadotrophin secretion. Prostaglandins. 1972 Jan;1(1):3–20. doi: 10.1016/0090-6980(72)90061-5. [DOI] [PubMed] [Google Scholar]
- Philipp-Dormston W. K., Siegert R. Adenosine 3',5'-cyclic monophosphate in rabbit cerebrospinal fluid during fever induced by E. coli-endotoxin. Med Microbiol Immunol. 1975;161(1):11–13. doi: 10.1007/BF02120765. [DOI] [PubMed] [Google Scholar]
- Philipp-Dormston W. K., Siegert R. Fever produced in rabbits by N6,O2-dibutyryl adenosine 3',5'-cyclic monophosphate. Experientia. 1975 Apr 15;31(4):471–472. doi: 10.1007/BF02026387. [DOI] [PubMed] [Google Scholar]
- Philipp-Dormston W. K., Siegert R. Identification of prostaglandin E by radioimmunoassay in cerebrospinal fluid during endotoxin fever. Naturwissenschaften. 1974 Mar;61(3):134–135. doi: 10.1007/BF00606298. [DOI] [PubMed] [Google Scholar]
- Philipp-Dormston W. K., Siegert R. Plasma prostaglandins of the E and F series in rabbits during fever induced by Newcastle disease virus, E. coli-endotoxin, or endogenous pyrogen. Z Naturforsch C. 1974 Nov-Dec;29(11-12):773–776. doi: 10.1515/znc-1974-11-1221. [DOI] [PubMed] [Google Scholar]
- Philipp-Dormston W. K., Siegert R. Prostaglandins of the E and F series in rabbit cerebrospinal fluid during fever induced by Newcastle disease virus, E. coli-endotoxin, or endogenous pyrogen. Med Microbiol Immunol. 1974 Jun 19;159(4):279–284. doi: 10.1007/BF02123737. [DOI] [PubMed] [Google Scholar]
- 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]
- SIEGERT R., BRAUNE P. THE PYROGENS OF MYXOVIRUSES. I. INDUCTION OF HYPERTHERMIA AND ITS TOLERANCE. Virology. 1964 Oct;24:209–217. doi: 10.1016/0042-6822(64)90106-0. [DOI] [PubMed] [Google Scholar]
- STEINBERG D., VAUGHAN M., NESTEL P. J., STRAND O., BERGSTROEM S. EFFECTS OF THE PROSTAGLANDINS ON HORMONE-INDUCED MOBILIZATION OF FREE FATTY ACIDS. J Clin Invest. 1964 Aug;43:1533–1540. doi: 10.1172/JCI105030. [DOI] [PMC free article] [PubMed] [Google Scholar]
- SUTHERLAND E. W., OYE I., BUTCHER R. W. THE ACTION OF EPINEPHRINE AND THE ROLE OF THE ADENYL CYCLASE SYSTEM IN HORMONE ACTION. Recent Prog Horm Res. 1965;21:623–646. [PubMed] [Google Scholar]
- Siegert R., Philipp-Dormston W. K., Radsak K., Menzel H. Inhibition of Newcastle disease virus-induced fever in rabbits by cycloheximide. Arch Virol. 1975;48(4):367–373. doi: 10.1007/BF01317435. [DOI] [PubMed] [Google Scholar]
- Siegert R., Pollmann W., Shu H. L. Zur chemischen Natur des endogenen, durch Myxovieren induzierten Pyrogens. Z Naturforsch B. 1967 Mar;22(3):320–323. [PubMed] [Google Scholar]
- Siegert R., Shu H. L., Pollmann W., Menzel H. Untersuchungen über Viruspyrogene. 1. Versuche zur Abtrennung des pyrogenen Prinzips von Myxoviren. Z Naturforsch B. 1967 Feb;22(2):155–158. [PubMed] [Google Scholar]
- THE PATHOGENESIS of fever. Am J Med. 1955 Mar;18(3):351–353. doi: 10.1016/0002-9343(55)90216-3. [DOI] [PubMed] [Google Scholar]
- Táborský I. Effect of cycloheximide on in vitro formation of rabbit granulocyte pyrogen induced with influenza A-PR8 virus or endotoxin. Acta Virol. 1972 Sep;16(5):376–381. [PubMed] [Google Scholar]
- Vane J. R. Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nat New Biol. 1971 Jun 23;231(25):232–235. doi: 10.1038/newbio231232a0. [DOI] [PubMed] [Google Scholar]
- WESTPHAL O., NOWOTNY A., LUDERITZ O., HURNI H., EICHENBERGER E., SCHONHOLZER G. Die Bedeutung der Lipoid-Komponente (Lipoid A) für die biologischen Wirkungen bakterieller Endotoxine (Lipopolysaccharide). Pharm Acta Helv. 1958 Aug-Oct;33(8-10):401–411. [PubMed] [Google Scholar]
- Weiss B., Costa E. Regional and subcellular distribution of adenyl cyclase and 3',5'-cyclic nucleotide phosphodiesterase in brain and pineal gland. Biochem Pharmacol. 1968 Oct;17(10):2107–2116. doi: 10.1016/0006-2952(68)90185-8. [DOI] [PubMed] [Google Scholar]
