Effects of fluoxetine pretreatment on endotoxemia-induced hypothermia

Abstract

Systemic inflammation associated syndromes are linked to high mortality rates and remain a challenge in emergency medicine. The administration of lipopolysaccharide (LPS) mimics systemic inflammation in an experimental animal model that produces pro-inflammatory cytokines such as TNF-±, IL-1² and IL-6, in addition to changes in body temperature, such as fever and hypothermia, depending on LPS dose and ambient temperature. The high mortality resulting from severe cases of systemic inflammation and the compromise it causes makes essential that pathophysiological mechanisms involved are better understood to promote the discovery of new therapies. Our group has recently demonstrated that the central administration of serotonin (5-HT) has an anti-inflammatory and thermoregulatory effect in experimental model of inflammation. In this sense, we believe that the manipulation of the serotonergic pathway is a potential treatment target, with fluoxetine, a selective serotonin reuptake inhibitor (SSRI) drug, being a potential immunomodulator via serotonergic mechanisms. Therefore, the aim of this project is to evaluate the role of previous treatment with fluoxetine on neuroimmune parameters in animals with systemic inflammation. To evaluate its potential, rats will be pre-treated with fluoxetine for 7 days and submitted to endotoxemic shock induced by LPS on the eighth day of the experiment, when they will be euthanized to collect plasma, brain, spleen and brown adipose tissue. These samples will be collected for the dosage of splenic and serum anti- and pro-inflammatory cytokines, as well as PGE2 and PGD2 in the hypothalamus and plasma, in addition to measurement of internal body temperature, tail temperature (to calculate the Heat Loss) and O2 consumption (to measure thermogenesis without tremor) that will be performed during the experiment. In this sense, it is expected to expand knowledge on the changes observed during systemic inflammation and its consequences, especially regarding fluoxetine as a potential immunomodulatory agent.