Laboratory of Joint Pathophysiology and Inflammation, Department of Medicine C, Rabin Medical Center, Petach Tikva, Israel.
Neuroimmunomodulation. 2012;19(5):309-18. doi: 10.1159/000339109. Epub 2012 Jul 12.
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.
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.
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.
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.
先前的研究表明选择性 5-羟色胺再摄取抑制剂（SSRIs）可调节免疫系统功能。SSRIs 是治疗重度抑郁症（MDD）的首选药物。类风湿关节炎（RA）患者中 MDD 的发病率很高。本研究旨在评估 SSRIs 在 RA 大鼠模型中的免疫作用。
在 8 周龄的 Lewis 大鼠中诱导佐剂关节炎；在诱导后的第一组实验中，将 15.3 或 30.6mg/kg 的舍曲林每天注射到左后腿的踝关节。评估临床疾病活动，并将结果与未经治疗的 3 条腿以及在同一部位给予甲氨蝶呤（MTX）或仅给予载体的对照组进行比较。在第二组实验中，评估了 5、25 和 50mg/kg 每日口服舍曲林在相同大鼠模型中的作用。评估脾细胞活力和炎症介质。
与对照组相比，所有剂量的舍曲林治疗大鼠的临床关节炎均明显减轻，同时白细胞介素 10 水平显著升高，肿瘤坏死因子-α水平和环氧化酶-2 产物降低，且无淋巴毒性。与 RA 患者的一线治疗药物 MTX 相比，无显著差异。口服舍曲林在所有剂量下均具有显著的抗炎作用。无治疗×时间效应。
舍曲林在这种关节炎大鼠模型中的有益作用对其在人类中的应用具有临床意义。需要进行大规模的临床疗效试验。
