CONICET | Buscador de Institutos y Recursos Humanos

Serotonin (5-HT) is synthesized mainly in the gut and can regulateinnate and adaptive immune functions. Multiple inflammatory factors,such as infections, modulate 5-HT levels in the body. In thissense, antidepressants (as fluoxetine) that modify 5-HT availabilityalso affect inflammatory responses. However, its ability to reducethe severity of autoinflammatory diseases remains to be elucidated.This work aims to study the impact of 5-HT changes in the developmentof reactive arthritis (ReA). In our study model, mice deficient inTNF receptor 1 (TNFR1 KO) develop ReA as a sequela after infectionwith Yersinia enterocolitica (Ye). Thus, non-infected TNFR1KOand WT mice were euthanized, and the distal portion of the smallintestine was removed and evaluated by immunofluorescence withan anti-serotonin receptor (SERT) antibody. Serum samples wereadditionally assayed for 5-HT by HPLC. In addition, WT and TNFR1KO mice were orally infected with Ye O:3 (1-5x108 bacteria/mouse).From infection day, fluoxetine (20 mg/kg/day) or water (control) wasadministrated in the drinking water. The ReA was detected on day14, and the score was recorded. On day 21, mice were euthanized,and sera samples were taken for 5-HT levels evaluation. Besides,the joints were obtained for histopathological evaluation and cytokinesdetermination by ELISA. Our results indicate that non-infectedTNFR1 KO mice have a higher basal serum 5-HT level, althoughno significant differences are observed in the ileum SERT expression.On day 21, fluoxetine-treated mice showed lower serum 5-HTlevels and less clinical symptoms severity than controls. Although asignificant reduction in proinflammatory cytokines was not detected,the reduction in the clinical score was consistent with less histologicaldamage in the joints. To conclude, increased availability of 5-HTcontributes to the development of ReA; however, blockade of SERTwith fluoxetine and their consequent reduction in serum 5-HT canattenuate joint damage.