| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Lovelace Respiratory Research Institute, Inhalation Toxicology Laboratory, Albuquerque, New Mexico 87185
Inhibitors of cyclooxygenases prevent fever. The purpose of this study was to test the hypothesis that selective and dual inhibitors of the other enzyme systems of arachidonic acid oxygenation (i.e., lipoxygenase and epoxygenase) affect the time course or magnitude of fever in mice. Swiss Webster mice kept at 30°C ambient temperature were implanted with biotelemeters to monitor body temperature. Fever was induced by intraperitoneal injection of lipopolysaccharide at doses from 10 µg/kg to 2.5 mg/kg. Phenidone (20-30 mg/kg ip), a dual lipoxygenase and cyclooxygenase inhibitor, prevented fever in these mice, but esculetin (1-10 mg/kg ip), a selective inhibitor of lipoxygenases, did not affect fever. Intramuscular injection of nordihydroguaiaretic acid (10-20 mg/kg), a dual lipoxygenase and epoxygenase inhibitor, as well as SKF-525A (5 mg/kg ip) and clotrimazole (20 mg/kg im), inhibitors of the cytochrome P-450/epoxygenase pathway, augmented fever in mice. Indomethacin (5 mg/kg ip), an inhibitor of cyclooxygenase, suppressed the exacerbation of fever due to clotrimazole, suggesting that the epoxygenase inhibitor-induced potentiation of fever in mice is a prostaglandin-mediated effect. From this study, we hypothesize that the cytochrome P-450/epoxygenase branch of the arachidonate cascade is involved in antipyresis and in controlling the upper limit of fever.
endotoxin; temperature regulation; cytokines; cyclooxygenases; lipoxygenases; cytochrome P-450; indomethacin; phenidone; esculetin; nordihydroguaiaretic acid; SKF-525A; clotrimazole
This article has been cited by other articles:
|
|
 |
|
  S. J. Spencer, A. Mouihate, M. A. Galic, and Q. J. Pittman Central and peripheral neuroimmune responses: hyporesponsiveness during pregnancy J. Physiol., January 15, 2008; 586(2): 399 - 406. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. D. Bradford, J. D. Cotter, M. S. Thorburn, R. J. Walker, and D. F. Gerrard Exercise can be pyrogenic in humans Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2007; 292(1): R143 - R149. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Y. Rudaya, A. A. Steiner, J. R. Robbins, A. S. Dragic, and A. A. Romanovsky Thermoregulatory responses to lipopolysaccharide in the mouse: dependence on the dose and ambient temperature Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2005; 289(5): R1244 - R1252. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Zuo, F. L. Christofi, V. P. Wright, S. Bao, and T. L. Clanton Lipoxygenase-dependent superoxide release in skeletal muscle J Appl Physiol, August 1, 2004; 97(2): 661 - 668. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Islam, R. F. Frye, T. J. Richards, I. Sbeitan, S. S. Donnelly, P. Glue, S. S. Agarwala, and J. M. Kirkwood Differential Effect of IFN{alpha}-2b on the Cytochrome P450 Enzyme System: A Potential Basis of IFN Toxicity and Its Modulation by Other Drugs Clin. Cancer Res., August 1, 2002; 8(8): 2480 - 2487. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. J. Roman P-450 Metabolites of Arachidonic Acid in the Control of Cardiovascular Function Physiol Rev, January 1, 2002; 82(1): 131 - 185. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Kozak, M. J. Kluger, A. Kozak, M. Wachulec, and K. Dokladny Role of cytochrome P-450 in endogenous antipyresis Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2000; 279(2): R455 - R460. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
