SSRIs exhibit anti-inflammatory effects and may provide drug development opportunities for RA
October 10, 2015
In the current study, researchers used a CIA mouse model due to the similarities to human RA, including synovitis, bone erosion and pannus formation. At the onset of arthritis, mice were treated daily for 7 days with a dose of 10 or 25 mg/kg of fluoxetine and 25 mg/kg of citalopram. At the lower dose of fluoxetine the mice showed a small reduction in the clinical score (a combined measure of redness, swelling and joint mobility/deformity) and a slower increase in paw swelling. At a dose of 25 mg/kg, fluoxetine halted disease progression and no further elevation was noted in the clinical score or paw swelling. "We observed reduced inflammation, reduced cartilage and bone erosion, and a preservation of the joint structure in the mice treated with a higher dose of fluoxetine," commented Dr. Sacre. Citalopram was not as effective as fluoxetine at inhibiting disease progression in this model.
Researchers also observed a decrease in cytokine production from cultures of human RA synovial joint tissues that were treated with SSRIs. Toll-like receptors (TLRs) are strong activators of immune cells leading to the production of cytokines that can induce inflammation. Fluoxetine was found to inhibit the activation of TLRs more effectively than citalopram.
"While the SSRIs effectively target TLRs contributing to inflammation and could provide therapeutic benefit in RA, they are not ideal candidates to progress into clinical trials," concluded Dr. Sacre. The levels of the SSRIs required to halt disease progression are higher than normally prescribed for standard treatment (depression in humans). "Our data suggests that effective inhibition of RA would require levels of the drugs higher than the safe therapeutic dosages." The authors suggest further study of the role of TLRs in chronic inflammation may uncover drugs that offer an effective treatment of RA in the future.