Recent data has signaled that in addition to its therapeutic indications as antidepressant and analgesic, amitriptyline (AM) exerts anti-inflammatory effects in humans and experimental animal models of acute inflammation. We tested the hypothesis that this compound could also modulate the chronic inflammatory process induced by synthetic matrix in mice. Polyether-polyurethane sponge disks were implanted subcutaneously in 9-week-old male C57BL/6 mice. The animals received by oral gavage 5.0 mg/kg of amitriptyline for seven consecutive days in two treatment regimens. In the first series, the treatment was initiated on the day of surgery and the implants removed at day 7 post-implantation. For the assessment of the effect of amitriptyline on chronic inflammation, the treatment was initiated 7 days post-implantation and the sponge discs removed 14 after implantation. The inflammatory markers evaluated, myeloperoxidase - MPO, nitrite content, IL-6, IFN-γ, TNF-α, CXCL1 and CCL2 levels, and NF-κB transcription factor activation were reduced in implants when the treatment began 7 days post-implantation (chronic inflammation). In contrast, only mast cell number, MPO activity and activation of NF-κB pathway decreased when the treatment began soon after implantation (sub-acute inflammation) in 7-day old implants. The anti-inflammatory effects of amitriptyline described here, extend its range of actions as a potential agent able to attenuate long-term inflammatory processes.

最近的数据表明，除了作为抗抑郁药和镇痛药的治疗适应症外，阿米替林 (AM) 还在人类和急性炎症实验动物模型中发挥抗炎作用。我们测试了这种化合物还可以调节小鼠合成基质诱导的慢性炎症过程的假设。将聚醚聚氨酯海绵盘植入 9 周龄雄性 C57BL/6 小鼠的皮下。在两种治疗方案中，动物连续 7 天通过口服强饲法接受 5.0 mg/kg 阿米替林。在第一个系列中，治疗在手术当天开始，植入物在植入后第 7 天移除。为了评估阿米替林对慢性炎症的影响，植入后 7 天开始治疗，植入后 14 天取出海绵盘。评估的炎症标志物、髓过氧化物酶 - MPO、亚硝酸盐含量、IL-6、IFN-γ、TNF-α、CXCL1 和 CCL2 水平以及 NF-κB 转录因子激活在植入后 7 天开始治疗时降低。慢性炎症）。相比之下，在 7 天大的植入物植入后不久开始治疗（亚急性炎症）时，只有肥大细胞数量、MPO 活性和 NF-κB 通路的激活降低。这里描述的阿米替林的抗炎作用扩大了其作为能够减轻长期炎症过程的潜在药物的作用范围。当植入后 7 天开始治疗（慢性炎症）时，植入物中的 NF-κB 转录因子激活降低。相比之下，在 7 天大的植入物植入后不久开始治疗（亚急性炎症）时，只有肥大细胞数量、MPO 活性和 NF-κB 通路的激活降低。这里描述的阿米替林的抗炎作用扩大了其作为能够减轻长期炎症过程的潜在药物的作用范围。当植入后 7 天开始治疗（慢性炎症）时，植入物中的 NF-κB 转录因子激活降低。相比之下，在 7 天大的植入物植入后不久开始治疗（亚急性炎症）时，只有肥大细胞数量、MPO 活性和 NF-κB 通路的激活降低。这里描述的阿米替林的抗炎作用扩大了其作为能够减轻长期炎症过程的潜在药物的作用范围。