Immunomodulatory effect of sertraline in a rat model of rheumatoid arthritis.
OBJECTIVE
Previous studies suggest that selective serotonin reuptake inhibitors (SSRIs) modulate immune system functionality. SSRIs are the preferred treatment for major depressive disorder (MDD). A high rate of MDD is observed in rheumatoid arthritis (RA) patients. The aim of this study was to evaluate immunological effects of SSRIs in a rat model of RA.


METHODS
Adjuvant arthritis was induced in 8-week-old Lewis rats; in the first set of experiments following the induction, 15.3 or 30.6 mg/kg of sertraline was daily injected into the ankle joint of the left rear leg. Clinical disease activity was evaluated and the findings compared with the 3 untreated legs and with control groups given methotrexate (MTX) or vehicle only at the same site. In a second set of experiments, the effect of 5, 25 and 50 mg/kg daily oral sertraline was evaluated in the same rat model. Splenocyte viability and inflammatory mediators were evaluated.


RESULTS
The sertraline-treated rats showed a significant reduction in clinical arthritis compared to controls, at all doses given, accompanied by a significant increase in interleukin 10 and a decrease in tumor necrosis factor-α levels and cycloxygenase-2 production, without lymphotoxicity. There was no significant difference from MTX, the first-line treatment for RA patients. Oral sertraline had a significant anti-inflammatory effect at all doses. There was no treatment × time effect.


CONCLUSIONS
The beneficial effects of sertraline in this rat model of arthritis have clinical implications for its use in humans. Large-scale clinical efficacy trials are needed.
Laboratory of Joint Pathophysiology and Inflammation, Department of Medicine C, Rabin Medical Center, Petach Tikva, Israel. ehudb@clalit.org.il
Ehud
E
Baharav
Meytal
M
Bar
Michal
M
Taler
Irit
I
Gil-Ad
Leon
L
Karp
Abraham
A
Weinberger
Avraham
A
Weizman
D000704:Analysis of Variance; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology*; D003208:Concanavalin A / Q000276:immunology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003601:Cytotoxicity Tests, Immunologic; D004185:Disability Evaluation; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D005620:Freund's Adjuvant / Q000633:toxicity; D007155:Immunologic Factors / Q000627:therapeutic use*; D008727:Methotrexate / Q000627:therapeutic use; D051381:Rats; D011917:Rats, Inbred Lew; D020280:Sertraline / Q000627:therapeutic use*; D013154:Spleen / Q000187:drug effects / Q000276:immunology; D013936:Thymidine / Q000378:metabolism
D016207:Cytokines; D007155:Immunologic Factors; D003208:Concanavalin A; D005620:Freund's Adjuvant; D051546:Cyclooxygenase 2; D020280:Sertraline; D013936:Thymidine; D008727:Methotrexate