HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 290/5/R1262    most recent 00724.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (11) Citing Articles via Google Scholar Google Scholar Articles by Li, Z. Articles by Blatteis, C. M. Search for Related Content PubMed PubMed Citation Articles by Li, Z. Articles by Blatteis, C. M.

CALL FOR PAPERS
Physiology and Pharmacology of Temperature Regulation

Kupffer cell-generated PGE₂ triggers the febrile response of guinea pigs to intravenously injected LPS

Department of Physiology, University of Tennessee Health Science Center, Memphis, Tennessee

Submitted 11 October 2005 ; accepted in final form 23 December 2005

Because the onset of fever induced by intravenously (iv) injected bacterial endotoxic lipopolysaccharides (LPS) precedes the appearance in the bloodstream of pyrogenic cytokines, the presumptive peripheral triggers of the febrile response, we have postulated previously that, in their stead, PGE₂ could be the peripheral fever trigger because it appears in blood coincidentally with the initial body core temperature (T_c) rise. To test this hypothesis, we injected Salmonella enteritidis LPS (2 µg/kg body wt iv) into conscious guinea pigs and measured their plasma levels of LPS, PGE₂, TNF-, IL-1, and IL-6 before and 15, 30, 60, 90, and 120 min after LPS administration; T_c was monitored continuously. The animals were untreated or Kupffer cell (KC) depleted; the essential involvement of KCs in LPS fever was shown previously. LPS very promptly (<10 min) induced a rise of T_c that was temporally correlated with the elevation of plasma PGE₂. KC depletion prevented the T_c and plasma PGE₂ rises and slowed the clearance of LPS from the blood. TNF- was not detectable in plasma until 30 min and in IL-1 and IL-6 until 60 min after LPS injection. KC depletion did not alter the times of appearance or magnitudes of rises of these cytokines, except TNF-, the maximal level of which was increased approximately twofold in the KC-depleted animals. In a follow-up experiment, PGE₂ antiserum administered iv 10 min before LPS significantly attenuated the febrile response to LPS. Together, these results support the view that, in guinea pigs, PGE₂ rather than pyrogenic cytokines is generated by KCs in immediate response to iv LPS and triggers the febrile response.

fever; tumor necrosis factor-; interleukin-1; interleukin-6; liver; complement

This article has been cited by other articles:

				Y. Ootsuka, W. W. Blessing, A. A. Steiner, and A. A. Romanovsky Fever response to intravenous prostaglandin E2 is mediated by the brain but does not require afferent vagal signaling Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2008; 294(4): R1294 - R1303. [Abstract] [Full Text] [PDF]

				C. Feleder, V. Perlik, and C. M. Blatteis Preoptic norepinephrine mediates the febrile response of guinea pigs to lipopolysaccharide Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2007; 293(3): R1135 - R1143. [Abstract] [Full Text] [PDF]

				C. Feleder, V. Perlik, and C. M. Blatteis Preoptic nitric oxide attenuates endotoxic fever in guinea pigs by inhibiting the POA release of norepinephrine Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2007; 293(3): R1144 - R1151. [Abstract] [Full Text] [PDF]

				A. Greis, J. Murgott, S. Rafalzik, R. Gerstberger, T. Hubschle, and J. Roth Characterization of the febrile response induced by fibroblast-stimulating lipopeptide-1 in guinea pigs Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2007; 293(1): R152 - R161. [Abstract] [Full Text] [PDF]

				A. A. Romanovsky Thermoregulation: some concepts have changed. Functional architecture of the thermoregulatory system Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2007; 292(1): R37 - R46. [Abstract] [Full Text] [PDF]