Sickness behavior em camundongos pré-tratados com inibidor da HMG-CoA Redutase

Abstract

Sickness behavior is the term used to define the set of behavioral changes that are triggered during an infectious process. Furthermore, these changes are considered the animal's adaptive responses in order to fight the infection, providing thereby an environment suitable for the establishment of an effective and unfavorable immune response to the pathogen. Several studies have addressed the pleiotropic effects of simvastatin, ie, effects that are beyond their hypocholesterolemic function. Among these effects, we can mention its antioxidant, anti-inflammatory, immunomodulatory and anti-thrombogenic action. Based on these assertions, the aim of this study was to investigate the influence of simvastatin on the sickness behavior. Initially, we tested doses of 100, 200 and 500 ug / kg of lipopolysaccharide (LPS), 2, 6 and 24 hours after application. Then, the Swiss mice were pre-treated for seven days with vehicle or Simvastatin 10 mg/kg or Simvastatin 40 mg/kg via gavage (p.o.) and on the eighth day, they received a dose of 200 µg/kg LPS or solution saline (i.p.) and behavioral responses were evaluated after 2 hours. In mice pretreated with simvastatin 10 mg/kg, no significant difference from the vehicle+LPS group in any of the apparatuses and analyzed parameters. However, in animals pretreated with simvastatin 40mg/kg there was a reduction of latency and increase in the number of crossings and the time spent in the light side in Bright-Dark Test, decreased floatings number in Forced Swimming and the immobility time in Tail Suspense Test and increased number of central, peripheral and total crossings and rearings in Open Field Test. The serum levels of the measured cytokines, we note that pre-treatment with simvastatin at doses of 10 and 40 mg/kg, was not able to attenuate the increase in TNF-α induced by LPS, however, the plasma concentrations of IL- 1β showed increased up to the pre-treatment with simvastatin 10 mg/kg and reduced when animals were pre-treated with simvastatin 40 mg/kg. In telemetry, we noticed a mild fever followed by hypothermia in animals that received LPS+vehicle and simvastatin 10+ LPS. Already in animals that received simvastatin 40+LPS, hypothermia observed but is not followed by fever. These results demonstrate that pre-treatment with simvastatin 40mg/kg (for 7 days) before application i.p. LPS is able to modify the behavioral responses to immune challenge, suggesting that this drug influences the manifestation of sickness behavior during endotoxemy.