Resumo:
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.
