Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Science, Smętna 12, PL 31-343 Kraków, Poland.
Pharmacol Rep. 2013;65(5):1237-46. doi: 10.1016/s1734-1140(13)71481-6.
Contact hypersensitivity (CHS) induced by a topical application of hapten - 2,4-dinitrofluorobenzene (DNFB), is a T cytotoxic (Tc)1-cell-mediated antigen-specific type of skin inflammation. Recently, it has been shown that antidepressant drugs inhibit the T helper (Th)1-mediated CHS reaction induced by picryl chloride. The aim of present study was to establish the effect of two-week desipramine or fluoxetine administration on the CHS reaction induced by DNFB.
Balb/c (H-2(d)) male mice were divided into six groups: 1) vehicle-treated negative control group; 2) desipramine-treated negative control group; 3) fluoxetine-treated negative control group; 4) vehicle-treated DNFB group (positive control group); 5) desipramine-treated DNFB group; 6) fluoxetine-treated DNFB group. T lymphocytes proliferation was determined by incorporation of [(3)H]-thymidine to DNA of concanavalin A stimulated cells. ELISA test was used for estimation of cytokines production.
The antidepressants significantly suppressed the CHS reaction mediated by Tc1 cells: desipramine by 55% and fluoxetine by 54% compared to the positive control. Moreover, the antidepressants decreased the proliferative activity of splenocytes and the ability of splenocytes to produce interleukin (IL)-6 and interferon (IFN)-γ and increased IL-10 production by the lymph node (LN) cells of DNFB-treated mice.
The results of the present study show that the Tc1-dependent reactivity to DNFB is significantly suppressed by antidepressant drugs, which suggests their inhibitory effect on Tc1 mediated immunity.
通过应用半抗原 2,4-二硝基氟苯（DNFB）于皮肤诱导产生接触超敏反应（CHS）是一种 T 细胞毒性（Tc）1 细胞介导的抗原特异性皮肤炎症。最近，研究表明抗抑郁药物可抑制由对氯苯二异氰酸酯诱导的 Th1 介导的 CHS 反应。本研究旨在确定两周的去甲丙咪嗪或氟西汀给药对 DNFB 诱导的 CHS 反应的影响。
将 Balb/c（H-2(d)）雄性小鼠分为六组：1）赋形剂处理的阴性对照组；2）去甲丙咪嗪处理的阴性对照组；3）氟西汀处理的阴性对照组；4）赋形剂处理的 DNFB 组（阳性对照组）；5）去甲丙咪嗪处理的 DNFB 组；6）氟西汀处理的 DNFB 组。通过[（3）H]-胸苷掺入到刀豆球蛋白 A 刺激的细胞 DNA 中来确定 T 淋巴细胞增殖。ELISA 试验用于估计细胞因子的产生。
与阳性对照组相比，抗抑郁药显著抑制了由 Tc1 细胞介导的 CHS 反应：去甲丙咪嗪抑制了 55%，氟西汀抑制了 54%。此外，抗抑郁药降低了脾细胞的增殖活性和脾细胞产生白细胞介素（IL）-6 和干扰素（IFN）-γ的能力，并增加了 DNFB 处理小鼠淋巴结（LN）细胞中 IL-10 的产生。
本研究结果表明，DNFB 诱导的 Tc1 依赖性反应明显受到抗抑郁药物的抑制，这表明它们对 Tc1 介导的免疫具有抑制作用。
