Brietzke Elisa, Stertz Laura, Fernandes Brisa Simões, Kauer-Sant'anna Marcia, Mascarenhas Marcello, Escosteguy Vargas Andréia, Chies José Artur, Kapczinski Flávio
Bipolar Disorder Program and Molecular Psychiatry Unit, Hospital de Clínicas de Porto Alegre, UFRGS, Brazil.
J Affect Disord. 2009 Aug;116(3):214-7. doi: 10.1016/j.jad.2008.12.001. Epub 2009 Feb 28.
The neurobiology of bipolar disorder is not completely understood. Cytokines have received increasing attention as potential mediators of the interaction with immune, neuroendocrine system and specific pathways involved in mood, energy, and activity control. Previous reports have suggested the association of mania and bipolar depression with a proinflammatory state. However, they did not compare cytokine levels in all phases of bipolar disorder.
Sixty-one bipolar patients were recruited for assessment of serum cytokine levels. Of these, 14 were in euthymic state, 23 and 24 were in manic and depressive episodes, respectively. A healthy comparison group included 25 healthy volunteers. Cytokines involved in Th1/Th2 balance, such as TNF-alpha, IL-2, IL-4, IL-6, IL-10, IFN-gamma, were examined by flow cytometry.
During mania, proinflammatory cytokines, IL-2, IL-4 and IL-6, were increased in comparison with healthy subjects. Patients in depressive episode showed only increased IL-6 levels. There were no significant differences in cytokine levels between patients in remission and healthy subjects, except for IL-4. Mood symptoms showed a positive correlation with IL-6 and IL-2.
These findings suggest that mania, and to a less extent, depression are associated with a proinflammatory state. These changes seem to be related to mood state, as changes in cytokine profile were more pronounced during acute episodes than in euthymia. This study provides further support to investigate the immune system as a target for future treatment development.
双相情感障碍的神经生物学机制尚未完全明确。细胞因子作为免疫、神经内分泌系统相互作用以及情绪、能量和活动控制相关特定通路的潜在介质，受到了越来越多的关注。既往报道提示躁狂发作及双相抑郁与促炎状态有关。然而，这些研究并未比较双相情感障碍各阶段的细胞因子水平。
招募61例双相情感障碍患者评估血清细胞因子水平。其中，14例处于心境正常状态，23例和24例分别处于躁狂发作和抑郁发作状态。选取25名健康志愿者作为健康对照组。通过流式细胞术检测参与Th1/Th2平衡的细胞因子，如肿瘤坏死因子-α（TNF-α）、白细胞介素-2（IL-2）、白细胞介素-4（IL-4）、白细胞介素-6（IL-6）、白细胞介素-10（IL-10）、干扰素-γ（IFN-γ）。
与健康受试者相比，躁狂发作期促炎细胞因子IL-2、IL-4和IL-6水平升高。抑郁发作期患者仅IL-6水平升高。缓解期患者与健康受试者的细胞因子水平除IL-4外无显著差异。情绪症状与IL-6和IL-2呈正相关。
这些发现提示躁狂发作以及程度较轻的抑郁发作与促炎状态有关。这些变化似乎与情绪状态相关，因为细胞因子谱的变化在急性发作期比心境正常期更为明显。本研究为将免疫系统作为未来治疗开发靶点的研究提供了进一步支持。
