Variable Antipyretic Effect of SC-58236, a Selective Cyclooxygenase (COX)-2 Inhibitor, in Rats

  • Eyup S. Akarsu
  • Soner Mamuk
  • Sibel Arat
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 525)


Fever is the most common body temperature (Tb) change accompanied to inflammation [1]. It has been reported that increased prostaglandin (PG) formation is generally essential for the genesis of fever [2]. The COX enzyme is required for PG synthesis. There are two isoforms of the COX enzyme as COX-1 and COX-2 [3]. Recent studies have suggested that COX- 2 isoenzyme is critical for the mediation of lipopolysaccharide (LPS)- induced fever in rodents [4,5]. But, our data did not support this suggestion [6]. Briefly, selective inhibitors of COX-2 and COX-1, either alone or in combination, did not inhibit the initiation of the fever component of LPS- induced dual Tb response in rats. It may be proposed that the model we used could be the source of this variance since we observed an initial hypothermia and subsequent fever by LPS at 50 γg/kg dose. The mechanisms of fever may have been determined by the pattern of the response implying that the fever as a component of dual response may have different characteristics than the fever, which develops without hypothermia. In this connection, a lower dose of LPS such as 2 γg/kg produces only fever in our experimental conditions [[7]]. Another source of variability might be related with LPS itself. We have reported that LPS causes serotype-specific Tb changes in rats [[7]]. Thus, it may be proposed that diverse signalling pathways might be activated depending on the dose or the serotype of LPS. In order to evaluate this proposal, the effects of COX-1 or COX-2 selective inhibitors (valeryl salicylate [VS] and SC-58236; respectively) on fever induced by low dose of two different serotype of LPSs were investigated in rats.


Febrile Response Dual Response Diverse Signalling Pathway Activate Alternative Pathway Fever Peak 
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Copyright information

© Springer Science+Business Media New York 2003

Authors and Affiliations

  • Eyup S. Akarsu
    • 1
  • Soner Mamuk
    • 1
  • Sibel Arat
    • 1
  1. 1.Faculty of Medicine, Department of Pharmacology and Clinical PharmacologyAnkara UniversityAnkaraTurkey

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