Serotonin: Important Key for Rheumatoid Arthritis

The symptoms and pathology of rheumatoid arthritis (RA) worsened in mice models, which were missing the enzyme needed for serotonin synthesis, according to findings published in The American Journal of Pathology.

Researchers from several hospitals in Paris, France tested mice models of RA that had a serotonin (5-hydroxytryptamine or 5-HT) synthesizer enzyme missing to demonstrate the effects on RA symptoms.

The investigators then examined the disease manifestations, including cartilage and bone destruction and activation of osteoclasts.

The team then compared those effects in RA mice to normal mice bred without the serotonin agonist in peripheral tissues.

The 5-HT was previously believed to act as a neurotransmitter in the central nervous system, the researchers said in a press release, but these findings indicated that 5-HT has additional functions in the periphery.

The number and activity levels of the osteoclasts in RA mice were higher in the 5 HT deficient mice than in the mice without the deficiency, the researchers reported.

As such, the mice with experimentally induced RA with a serotonin deficit experienced worse symptoms than in the RA mice without the deficit. They also found that more bone resorption was found at affected joints as well as remote sites in these mice. Additionally, they said, serotonin or the compounds that activated serotonin receptors could decrease some of the RA symptoms.

“Our study highlights that 5-HT has a direct immunoregulatory role in arthritis,” said co-lead investigator Marie-Christine de Vernejoul in the statement. “The development of treatments targeting 5-HT or 5-HT receptors could represent an exciting prospect to regulate the immune response in RA and open new perspectives to improve the therapeutic options for patients.”

The researchers also observed cytokine changes in the paws of the serotonin deficient mice: higher IL 17, higher TNF alpha and lower IL 4. The mice seemed to have unbalanced T cell subtypes such as regulatory T cells (Treg) and T 17 lymphocytes.

“Altogether, our data show that 5-HT deficient mice are characterized by a relative, dampened expansion of Treg associated with an enhanced shift toward a Th17 phenotype, a situation previously described in patients with arthritis,” added co-lead investigator Francine Côté.

The researchers hope that in the future, they are able to conduct experiments using cell cultures to further investigate the balance of Treg and Th 17 cells and how they are disrupted by the addition or subtraction of serotonin and serotonin receptor cells. They believed this link could be the key in discovering exactly what role serotonin plays in RA and that these receptors could one day be a therapeutic target for RA patients.