Abstract.
Objective: Compare the antipyretic effects of dipyrone and indomethacin.¶Materials and methods: Fever was induced in rats by i.v. LPS or i.c.v. interleukins (IL), prostaglandins (PG), arachidonic acid (AA), pre-formed pyrogenic factor (PFPF), tumour necrosis factor-α (TNF-α) or corticotrophin releasing hormone (CRH). Dipyrone and indomethacin were administered i.p., arginine vasopressin V1-receptor antagonist, d(CH2)5 Tyr(Me)AVP, into the ventral septal area. Cyclooxygenase (COX-1/-2) blocking activity was assessed in transfected COS-7 cells. CRH release from isolated hypothalami was determined by ELISA.¶Results: Indomethacin or dipyrone reduced LPS, IL-1β, IL-6 or TNF-α induced fever and CRH release from rat hypothalamus. Only dipyrone inhibited IL-8, PFPF or PGF2α fever. Only indomethacin inhibited fever induced by AA or IL-1β plus AA. Neither antipyretic affected fever caused by PGE2 or CRH. d(CH2)5Tyr(Me)AVP only blocked antipyresis induced by indomethacin. Dipyrone at a very high concentration (10 mM) inhibited only COX-1, while indomethacin (0.1 μM) blocked COX-1 and COX-2 in COS-7 cells.¶Conclusion: The antipyretic effect of dipyrone differs from that of indomethacin in that it does not depend on AVP release or inhibition of PG synthesis.
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Received 14 December 2000; returned for revision 18 June 2001; accepted by M. J. Parnham 1 October 2001
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de Souza, G., Cardoso, R., Melo, M. et al. A comparative study of the antipyretic effects of indomethacin and dipyrone in rats. Inflamm. res. 51, 24–32 (2002). https://doi.org/10.1007/PL00000278
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DOI: https://doi.org/10.1007/PL00000278