Simvastatin attenuated sickness behavior and fever in a murine model of endotoxemia.
AIMS
During illnesses caused by infectious disease, a suite of brain-mediated responses called sickness syndrome occurs, triggering behavioral and physiological (fever) changes. Simvastatin is widely used as a lipid-lowering medication that has beneficial immunomodulatory properties. This study investigated the effects of simvastatin in a mouse model of sickness syndrome by systemic administration of lipopolysaccharide (LPS).


MAIN METHODS
Male mice were pretreated with vehicle or simvastatin (40 mg/kg, p.o.) for 7 days and received LPS (200 μg/kg, i.p.) or sterile saline. We investigated the behavioral effects in male mice 2 h after LPS administration using tests screening for depressive-like behavior and locomotor activity alterations. Changes in body temperature were measured by biotelemetry probe preimplanted in the peritoneal cavity to evaluate the effect of simvastatin on the thermoregulatory response during immunological challenge.


KEY FINDINGS
Pretreatment with simvastatin blunted most of the assessed parameters related to sickness syndrome, including depressive-like behavior and depressed locomotor activity, and attenuated LPS-induced fever. These data are consistent with simvastatin promoting alterations in peripheral febrigenic signaling (plasma levels of TNF-α, IL-1β, and IL-10).


SIGNIFICANCE
Our data provide further evidence of the capacity of simvastatin to attenuate sickness behavior and fever induced by immunological challenge through a mechanism related to changes in the profile of cytokine production.
['Oliveira|Merelym K|MK|', 'Dos Santos|Rafaela S|RS|', 'Cabral|Layla D M|LDM|', 'Vilela|Fabiana C|FC|', 'Giusti-Paiva|Alexandre|A|']
D000818:Animals D004195:Disease Models, Animal D019446:Endotoxemia D005334:Fever D006801:Humans D055809:Illness Behavior D008297:Male D051379:Mice D019821:Simvastatin
Lipopolysaccharide Cytokines Inflammation Statins Thermoregulation