Diacerein decreases TNF-alpha and IL-1beta levels in peritoneal fluid and prevents Baker's yeast-induced fever in young rats.

OBJECTIVE: To investigate the effect of diacerein, an anti-inflammatory drug, on body temperature and protocols of fever induction in male Wistar rats. METHODS: The effect of diacerein (5.0 mg/kg, s.c.) on rectal temperature (T (R)) changes induced by Baker's yeast (0.135 g/kg, i.p.) and PGE(2) (10 ng/animal, i.t.) was evaluated. T (R) changes were recorded over time. The leukocyte count and TNF-alpha and IL-1beta content were evaluated in the peritoneal fluid by means of optical microscopy and enzyme immunoassay (ELISA kits), respectively. RESULTS: The administration of diacerein to febrile animals attenuated Baker's yeast-induced fever but did not alter prostaglandin E(2)-induced fever. Diacerein prevented the development of Baker's yeast-induced fever and significantly attenuated the increase in peritoneal leukocytes and decreased IL-1beta and TNF-alpha levels in peritoneal fluid. CONCLUSIONS: These data suggest that diacerein partially protects against Baker's yeast-induced fever and peritoneal leukocyte migration, and indicate that this effect appears to be due to inhibition of release of cytokines (such as TNF-alpha and IL-1beta).

Baker yeast-induced fever in young rats: characterization and validation of an animal model for antipyretics screening.

In this study we describe a low-cost and reliable method for inducing fever in young male rats (28-30 days of age, 75-90 g), which seems suitable for the screening of new antipyretics. The effects of temperature measuring procedure-induced stress on the basal rectal temperature and on Baker yeast-induced hyperthermia was assessed. Rectal temperature (T) was recorded every hour for 12 h (07:00-19:00 h) with a lubricated thermistor probe. The animals were injected intraperitoneally with baker yeast (0.25, 0.135, 0.05 g/kg) or the equivalent volume of saline at 7:00 h. The administration of 0.135 g/kg baker yeast induced a sustained increase in rectal temperature for 4 h. Classical (dipyrone and acetaminophen) and novel (MPCA and FPCA) antipyretics, at doses that had no effect per se, reverted baker yeast-induced fever. The method presented induces a clear-cut fever, which is reverted by antipyretics commonly used in human beings and selected novel antipyretics in small animals. The method also allows antipyretic evaluation with low amount of drugs, due to the use of small animals and to the small variability of the pyretic response, which ultimately causes a significant reduction in the number of animals necessary for antipyretic evaluation. Therefore, this study describes an animal model of fever that is not only advantageous from the economical and technical point of view, but that also bears ethical concerns.