Endocannabinoids, through opioids and prostaglandins, contribute to fever induced by key pyrogenic mediators.
This study aims to explore the contribution of endocannabinoids on the cascade of mediators involved in LPS-induced fever and to verify the participation of prostaglandins and endogenous opioids in fever induced by anandamide (AEA). Body temperature (Tc) of male Wistar rats was recorded over 6h, using a thermistor probe. Cerebrospinal fluid concentration of PGE2 and β-endorphin were measured by ELISA after the administration of AEA. Intracerebroventricular administration of the CB1 receptor antagonist AM251 (5μg, i.c.v.), reduced the fever induced by IL-1β (3ng, i.c.v.), TNF-α (250ng, i.c.v.), IL-6 (300ng, i.c.v.), corticotrophin release factor (CRH; 2.5μg, i.c.v.) and endothelin (ET)-1 (1pmol, i.c.v.), but not the fever induced by PGE2 (250ng, i.c.v.) or PGF2α (250ng, i.c.v.). Systemic administration of indomethacin (2mgkg(-1), i.p.) or celecoxib (5mgkg(-1), p.o.) reduced the fever induced by AEA (1μg, i.c.v.), while naloxone (1mgkg(-1), s.c.) abolished it. The increases of PGE2 and β-endorphin concentration in the CSF induced by AEA were abolished by the pretreatment of rats with AM251. These results suggest that endocannabinoids are intrinsically involved in the pyretic activity of cytokines (IL-1β, TNF-α, IL-6), CRH and ET-1 but not the PGE2 or PGF2α induced fevers. However, anandamide via CB1 receptor activation induces fever that is dependent on the synthesis of prostaglandin and opioids.
Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, University of São Paulo, Ribeirão Preto, SP, Brazil; Faculty of Nursing, Federal University of Mato Grosso of Sul, Coxim, MS, Brazil. Electronic address: danfraga79@gmail.com.
Daniel
D
Fraga
Laboratory of Neuropathic Pain, Department of Pharmacology, Institute of Biomedical Sciences, São Paulo, Brazil.
Cristiane I S
CIS
Zanoni
Department of Pharmacology, Federal University of Paraná, PR, Brazil.
Aleksander R
AR
Zampronio
Biology Institute, University of Campinas, UNICAMP, Campinas, SP, Brazil.
Carlos A
CA
Parada
Department of Pharmacology, Biological Science Center, Federal University of Santa Catarina, Brazil.
Giles A
GA
Rae
Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, University of São Paulo, Ribeirão Preto, SP, Brazil.
Glória E P
GEP
Souza
D000818:Animals; D001095:Arachidonic Acids / Q000008:administration & dosage / Q000502:physiology*; D001831:Body Temperature / Q000187:drug effects; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage; D016207:Cytokines / Q000008:administration & dosage / Q000502:physiology*; D063388:Endocannabinoids / Q000008:administration & dosage / Q000502:physiology*; D019332:Endothelin-1 / Q000008:administration & dosage; D005334:Fever / Q000139:chemically induced / Q000503:physiopathology*; D053583:Interleukin-1beta / Q000008:administration & dosage / Q000502:physiology; D015850:Interleukin-6 / Q000008:administration & dosage / Q000502:physiology; D008297:Male; D009270:Naloxone / Q000008:administration & dosage; D009292:Narcotic Antagonists / Q000008:administration & dosage; D010880:Piperidines / Q000008:administration & dosage; D053284:Polyunsaturated Alkamides / Q000008:administration & dosage; D011453:Prostaglandins / Q000008:administration & dosage / Q000502:physiology*; D011720:Pyrazoles / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000502:physiology; D001615:beta-Endorphin / Q000134:cerebrospinal fluid*
D001095:Arachidonic Acids; D016207:Cytokines; D063388:Endocannabinoids; D019332:Endothelin-1; D053583:Interleukin-1beta; D015850:Interleukin-6; D009292:Narcotic Antagonists; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D011453:Prostaglandins; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D014409:Tumor Necrosis Factor-alpha; D009270:Naloxone; C103505:AM 251; D001615:beta-Endorphin; D003346:Corticotropin-Releasing Hormone; C078814:anandamide
Anandamide; Cytokines; Endocannabinoids; Fever; Prostaglandins; β-Endorphin