There are accumulating reports regarding poor response to common antidepressant therapy. Antidepressant resistance is often linked to inflammatory system activation and patients displaying inflammation prior to the treatment are less responsive to antidepressants. We hypothesized that the inefficacy of antidepressant therapy in some patients may be attributable to the drugs’ inflammatory mode of action, which has been overlooked because of their substantial therapeutic benefit. Bupropion is a commonly prescribed antidepressant that is often used to treat seasonal affective disorders as well. Nevertheless, research suggests that bupropion causes inflammation and worsens depressive symptoms. Therefore, we investigated the impact of bupropion on cytokines of innate and adaptive immunity, as well as immune signaling pathways. We treated lipopolysaccharide (LPS)-stimulated human peripheral blood mononuclear cells (PBMCs) with different doses of bupropion. Pro-/anti-inflammatory cytokines [tumor necrosis factor alpha (TNFα), interleukin-1β (IL-1β), IL-17, and IL-10] were assessed at both transcriptional and translational levels as well as the involvement of JAK2 /STAT3, TLR2, and TLR4 signaling in this process. Bupropion reduced IL-17A, TNFα, and IL-1β protein levels in the cultures. Nonetheless, bupropion increased IL-1β (P < 0.0001), TNFα (P < 0.0001), and IL-17A (P < 0.05) mRNA levels. Treatment enhanced both IL-10 concentration (P < 0.0001) and gene expression (P < 0.0001). TLR2 (P < 0.0001), TLR4 (P < 0.0001), JAK2 (P < 0.0001), and STAT3 (P < 0.0001) gene expression also rose in response to bupropion. The findings imply that bupropion, particularly 50 μM and 100 μM, has pro-inflammatory effects and should be co-administered with anti-inflammatory medications, at least in patients with inflammatory conditions.

关于对普通抗抑郁药治疗反应不佳的报道越来越多。抗抑郁药耐药性通常与炎症系统激活有关，并且在治疗前表现出炎症的患者对抗抑郁药的反应较弱。我们假设一些患者抗抑郁治疗无效可能是由于药物的炎症作用模式，但由于其显着的治疗益处而被忽视。安非他酮是一种常用的抗抑郁药，也常用于治疗季节性情感障碍。尽管如此，研究表明安非他酮会引起炎症并加重抑郁症状。因此，我们研究了安非他酮对先天免疫和适应性免疫细胞因子以及免疫信号通路的影响。我们用不同剂量的安非他酮处理脂多糖 (LPS) 刺激的人外周血单核细胞 (PBMC)。在转录和翻译水平以及 JAK2 /此过程中的 STAT3、TLR2 和 TLR4 信号。安非他酮降低培养物中的 IL-17A、TNFα 和 IL-1β 蛋白水平。尽管如此，安非他酮增加了 IL-1β（和 TLR4 信号在这个过程中。安非他酮降低培养物中的 IL-17A、TNFα 和 IL-1β 蛋白水平。尽管如此，安非他酮增加了 IL-1β（和 TLR4 信号在这个过程中。安非他酮降低培养物中的 IL-17A、TNFα 和 IL-1β 蛋白水平。尽管如此，安非他酮增加了 IL-1β（P  < 0.0001)、TNFα ( P  < 0.0001) 和 IL-17A ( P  < 0.05) mRNA 水平。治疗增强了 IL-10 浓度 ( P  < 0.0001) 和基因表达 ( P  < 0.0001)。TLR2 ( P  < 0.0001)、TLR4 ( P  < 0.0001)、JAK2 ( P  < 0.0001) 和 STAT3 ( P  < 0.0001) 基因表达也随着对安非他酮的反应而升高。研究结果表明，安非他酮（尤其是 50 μM 和 100 μM）具有促炎作用，应与抗炎药物联合使用，至少在患有炎症的患者中如此。