Cyclooxygenase-independent mechanism of ibuprofen-induced antipyresis: the role of central vasopressin V-1 receptors

Autor(es)

Soares, Denis M. ^[1] ; Cristofoletti, Rodrigo ^[1] ; Melo, Miriam C. C. ^[1] ; Lindsey, Charles J. ^[2] ; Veiga-Souza, Fabiane H. ^[1] ; Fabricio, Aline S. C. ^[1] ; Souza, Gloria E. P. ^[1]

Afiliação do(s) autor(es)

^[1] USP, Farmacol Lab, Fac Ciencias Farmaceut Ribeirao Preto, BR-14040903 Ribeirao Preto, SP - Brazil

^[2] Univ Fed Sao Paulo, Dept Biofis, Escola Paulista Med, BR-01402000 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: FUNDAMENTAL & CLINICAL PHARMACOLOGY; v. 25, n. 6, p. 670-681, DEC 2011.
• Citações Web of Science: 4

Resumo

This study compared the antipyretic effects of ibuprofen and indomethacin regarding the efficacy in blocking fevers induced by lipopolysaccharide (LPS from E. coli) or pyrogenic mediators that act on prostaglandin (PG)-dependent and PG-independent pathways. The content of PGE(2) in the cerebrospinal fluid (CSF) and the dependence on central arginine vasopressin (AVP) release by both antipyretics were also compared during the reduction of LPS-induced fever. Finally, we investigated the effect of ibuprofen on hypothalamic cytokine content during LPS-induced fever. Ibuprofen (intraperitoneally, i.p.) dose-dependently inhibited the fever induced by LPS (intravenously, i.v.). Indomethacin (2 mg/kg) and ibuprofen (10 mg/kg) reduced the fever induced by i.c.v. injection of interleukin (IL)-1 beta, IL-6, tumor necrosis factor (TNF)-alpha, or arachidonic acid (AA). Ibuprofen, but not indomethacin, inhibited i.c.v. endothelin-1- and pre-formed pyrogenic factor (PFPF)-induced fever. Neither ibuprofen nor indomethacin affected fever by PGE(2), PGF(2 alpha), or corticotrophin-releasing factor (CRF); however, both reduced the CSF PGE(2) content after LPS. Bilateral injection of the AVP V(1) receptor antagonist d(CH(2))(5)Tyr(Me) AVP into the ventral septal area blocked both ibuprofen- and indomethacin-induced antipyresis. Ibuprofen did not modify the hypothalamic increase in either IL-1 beta or IL-6 induced by LPS. In conclusion, although the antipyretic effect of ibuprofen involves the blockage of central production of PGE(2) and the endogenous release of AVP, differently from low dose of indomethacin, ibuprofen not only reduced the fever induced by PGE(2)-dependent, but also, that induced by PGE(2)-independent endogenous pyrogens. Moreover, ibuprofen does not affect the hypothalamic synthesis/release of IL-1 beta and IL-6. (AU)

• Processo FAPESP: 08/10323-3 - Investigação dos mecanismos celulares e moleculares centrais envolvidos na febre induzida pela CCL3/MIP-1alpha
• Beneficiário: Denis de Melo Soares
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 99/12466-5 - Neuropeptídeos nas respostas de defesa e homeostase: receptores e vias neurais
• Beneficiário: Charles Julian Lindsey
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 97/09837-6 - Mecanismos e mediadores envolvidos na integração das respostas inflamatória e febril
• Beneficiário: Glória Emília Petto de Souza
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 02/02059-8 - Estudo dos efeitos antipiretico e antialgico do ibuprofeno em ratos.
• Beneficiário: Rodrigo Cristofoletti
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 00/12573-5 - Atividades pirogênica e hiperalgésica do fator pirogênico pré-formado em macrófagos (PFPF): os mediadores são os mesmos?
• Beneficiário: Fabiane Hiratsuka Veiga de Souza
• Modalidade de apoio: Bolsas no Brasil - Doutorado