Department of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany; Department of Cardiology and Angiology, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
Department of Cardiology and Angiology, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
J Psychiatr Res. 2018 Oct;105:95-102. doi: 10.1016/j.jpsychires.2018.08.017. Epub 2018 Sep 4.
Schizophrenia and major depression are associated with alterations in peripheral inflammatory markers, and anti-inflammatory therapy has been proposed as a promising add-on approach in the pharmacologic treatment of both disorders. Second-generation atypical antipsychotics are currently first-line drugs in the treatment of schizophrenia and are also used as augmentation strategies in treatment-resistant major depression. Furthermore, these drugs have been reported to exhibit distinct metabolic side effects and to influence inflammatory processes. In this study, we used ex vivo stimulation of primary human peripheral blood mononuclear cells (PBMC) from healthy blood donors with atypical antipsychotics olanzapine or aripiprazole to examine effects on cytokine production independent from metabolic side effects and disease status. Both olanzapine and aripiprazole stimulation decreased mRNA levels of IL-1β, IL-6, and TNF-α and resulted in diminished protein concentrations of IL-6 and TNF-α in conditioned medium of stimulated PBMC. A multiplex approach revealed additional downregulation of IL-2; MIP-1β and IP-10 secretion. Similarly, olanzapine and aripiprazole stimulation of the human monocytic cell line THP-1 resulted in a significant decrease in expression and secretion of IL-1β and TNF-α. Our results suggest that atypical antipsychotics directly influence immune cell function and thereby highlight the importance to factor in potential side effects of drugs routinely used in treatment of schizophrenia and major depression on inflammatory processes when considering anti-inflammatory drug therapy as an additional treatment option.
精神分裂症和重度抑郁症与外周炎症标志物的改变有关，抗炎治疗已被提议作为这两种疾病药物治疗的一种有前途的附加方法。第二代非典型抗精神病药目前是治疗精神分裂症的一线药物，也被用作治疗抵抗性重度抑郁症的增效策略。此外，这些药物已被报道具有明显的代谢副作用，并影响炎症过程。在这项研究中，我们使用来自健康献血者的外周血单个核细胞（PBMC）的体外刺激与非典型抗精神病药奥氮平和阿立哌唑，以检查独立于代谢副作用和疾病状态对细胞因子产生的影响。奥氮平和阿立哌唑刺激均降低了 IL-1β、IL-6 和 TNF-α 的 mRNA 水平，并导致刺激 PBMC 条件培养基中 IL-6 和 TNF-α 的蛋白浓度降低。多重分析方法显示 IL-2、MIP-1β 和 IP-10 的分泌也有额外下调。同样，奥氮平和阿立哌唑对人单核细胞系 THP-1 的刺激导致 IL-1β 和 TNF-α 的表达和分泌显著减少。我们的结果表明，非典型抗精神病药直接影响免疫细胞功能，因此在考虑将抗炎药物作为附加治疗选择时，当考虑抗炎药物治疗作为附加治疗选择时，必须考虑到常规用于治疗精神分裂症和重度抑郁症的药物的潜在副作用对炎症过程的影响。
