Variable Antipyretic Effect of SC-58236, a Selective Cyclooxygenase (COX)-2 Inhibitor, in Rats
- 139 Downloads
Fever is the most common body temperature (Tb) change accompanied to inflammation . It has been reported that increased prostaglandin (PG) formation is generally essential for the genesis of fever . The COX enzyme is required for PG synthesis. There are two isoforms of the COX enzyme as COX-1 and COX-2 . 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 . 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 []. Another source of variability might be related with LPS itself. We have reported that LPS causes serotype-specific Tb changes in rats []. 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.
KeywordsFebrile Response Dual Response Diverse Signalling Pathway Activate Alternative Pathway Fever Peak
Unable to display preview. Download preview PDF.
- 1.Kluger MJ.Fever Role of pyrogens and cryogens. Physiol Rev 1991; 71: 93–161.Google Scholar
- 8.Dogan MD, Ataoglu H, Akarsu ES. Polysaccharide components of exogenous pyrogens produce fever in rats. In: Gourine VN, ed. Basic and Applied Thermophysiology. Inst Physiol Natl Acad Sci Rep Belarus, 2000; pp: 26–29.Google Scholar