Submitted on June 23, 2008
Revised on February 17, 2009
Accepted on February 18, 2009
Characterization and Pharmacological Evaluation of Febrile Response on Zymosan-induced Arthritis in rats
Alexandre Kanashiro1, Andrea Carla Pessini1, Renes R. Machado2, David Do Carmo Malvar1, Fernando Armani Aguiar1, Denis Melo Soares1, Mariana L do Vale3, and Gloria Emilia Petto de Souza2*
1 University of São Paulo
2 University of Sao Paulo
3 Federal University of Ceará
* To whom correspondence should be addressed. E-mail: gepsouza{at}fcfrp.usp.br.
The present study investigated the febrile response in zymosan-induced arthritis as well as the increase in PGE2 concentration in the cerebrospinal fluid (CSF) along with the effects of antipyretic drugs on these responses in rats. Zymosan intra-articular (i.a.) injected at the dose of 0.5 mg did not affect the body core temperature (Tc) when compared to saline (control), whereas at doses of 1 and 2 mg, zymosan promoted a flattened increase in Tc and declined thereafter. The dose of 4 mg of zymosan was selected for further experiments because it elicited a marked and long lasting Tc elevation starting at 3 1/2 h, peaking at 5 1/2 h and remaining until 10 h. This temperature increase was preceded by a decrease in the tail skin temperature and hyperalgesia and edema in the knee joint. No febrile response was observed in the following days. In addition, zymosan-induced fever was not modified by the sciatic nerve excision. Zymosan increased PGE2 concentration in the CSF but not in the plasma. Oral pre-treatment with ibuprofen (5-20 mg kg-1), celecoxib (1-10 mg kg-1), dipyrone (60-240 mg kg-1) and paracetamol (100-200 mg kg-1) or subcutaneous injection of dexamethasone (0.25-1.0 mg kg-1) dose-dependently reduced or prevented the fever during the zymosan-induced arthritis. Celecoxib (5 mg kg-1), paracetamol (150 mg kg-1) and dipyrone (120 mg kg-1) decreased CSF PGE2 concentration and fever during zymosan-induced arthritis suggesting the involvement of PGE2 in this response.
