Avaliação do papel da serotonina na resposta de macrófagos murinos inoculados com Staphylococcus aureus e Escherichia coli

Abstract

Serotonin (5-hydroxytryptamine or 5-HT) modulates immune responses in immune cells, and this action occurs through the serotonergic system. This monoaminergic neurotransmitter acts on immune cells, coordinating the immune responses of macrophages, Natural killer (NK) cells, dendritic cells and lymphocytes, either inhibiting or stimulating them, but the effects of 5-HT specifically on different immune stimuli in specific tissues. Thus, the present study aimed to evaluate the effect of 5-HT on the immune response induced by inoculation of Staphylococcus aureus and Escherichia coli, in cultures of peritoneal and splenic macrophages from mice treated or not with serotonin. For this, mice of the C57BL6 lineage were used. The first group consisted of animals treated with 5-HT in vivo, where serotonin was administered intracerebroventricularly and after 30 minutes LPS was injected intraperitoneally, in order to induce local inflammation. The second group of sham animals underwent ICV surgery, however, only 0.1% ascorbic acid (vehicle) was administered and did not go through the inflammatory induction process. After surgery, peritoneal and splenic macrophages were extracted from the animals, using a specific protocol, and were incubated for 24 hours. The sham group was divided into two subgroups: macrophages treated with 5-HT in vitro and untreated macrophages. In vitro treated macrophages received different dosages of 5-HT (10-3 M, 10-6 M and 10-8 M) and were again incubated for 24 hours, while the subgroup of untreated macrophages did not undergo any type of contact with 5-HT. After the respective incubation period, macrophages treated in vivo, in vitro and untreated were infected with E. coli and S. aureus (positive control) or saline (negative control) and incubated again for 3 hours. After collection, the gene expression of the cytokines TNFα, IL-1β, IL-6 in the cells was carried out, as well as the dosage of hydrogen peroxide and nitric oxide in the supernatant. In general, macrophages obtained from animals treated in vivo with 5-HT and macrophages treated in vitro with 10-3 M and 10-6 M of 5-HT showed lower expressions of inflammatory markers when compared to macrophages without any type of treatment, in infections using E. coli and S. aureus, especially 10-3 which recorded this drop in all analyzes performed. The same effect was not observed with the in vitro treatment using 10-8 M 5-HT. Therefore, the results of the present study lead us to the conclusion that serotonin may be involved in the inhibition of components that regulate inflammation according to the type of infection to which it is exposed. Furthermore, modulation of serotonin in the inflammatory response indicates a possible anti-inflammatory potential of 5-HT. However, more studies need to be carried out to deeply evaluate the mechanisms involved in this process.