SSRIs Show Anti-Inflammatory Benefit in RA Models

Fluoxetine, citalopram findings point to possible role of Toll-like receptors in condition
By Eric Metcalf
HealthDay Reporter

FRIDAY, March 12 (HealthDay News) -- Fluoxetine and citalopram show an anti-inflammatory benefit in rheumatoid arthritis (RA) in laboratory experiments, with findings pointing toward endosomal Toll-like receptors (TLRs) as a target for therapy in the disease, according to research published in the March issue of Arthritis & Rheumatism.

Sandra Sacre, Ph.D., of the University of Sussex in Brighton, U.K., and colleagues analyzed data obtained from murine collagen-induced arthritis and a human ex vivo disease model of RA. Following therapeutic administration of fluoxetine and citalopram, the researchers sought to determine the anti-arthritic potential of these agents.

The researchers found that both treatments inhibited disease progression in the mice, but fluoxetine showed greater efficacy both in clinical and histological observations. In other testing, using human RA synovial membrane cell cultures, both drugs inhibited production of tumor necrosis factor, interleukin-6, and interferon-γ-inducible protein 10. They also inhibited signaling of TLRs 3, 7, 8, and 9. The authors write that TLRs respond to molecules that may be released during tissue inflammation.

"Fluoxetine and citalopram are not ideal candidates to be progressed into clinical trials, since our in vitro data suggest that effective inhibition would require levels above their safe therapeutic dosages," the authors conclude. "Nevertheless, these data in conjunction with our previous study support the concept of a contribution from endosomal TLRs to the chronic inflammation associated with the pathogenesis of RA and demonstrate the potential to selectively target these receptors with small molecules in the future for the effective treatment of RA."

One author reported a patent application related to this subject, and another reported financial relationships with Wyeth.

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