Bonaccorso S, Puzella A, Marino V, Pasquini M, Biondi M, Artini M, Almerighi C, Levrero M, Egyed B, Bosmans E, Meltzer H Y, Maes M
Psychiatric Hospital, University 'La Sapienza', Rome, Italy.
Psychiatry Res. 2001 Dec 15;105(1-2):45-55. doi: 10.1016/s0165-1781(01)00315-8.
Immunotherapy with interferon-alpha (IFNalpha) may induce depressive symptoms, anxiety and major depression when administered for at least 1-3 months at a dose of 3-10 MUI daily, twice or three times a week. Previously, it has been shown that immunotherapy with interleukin-2 (IL-2) significantly induces the cytokine network, as measured by increases in serum IL-6, IL-10 and the IL-2 receptor (IL-2R), and that the immunotherapy-induced changes in the cytokine network are significantly correlated with the increases in depression ratings. The main aim of this study was to examine the effects of immunotherapy with IFNalpha on the cytokine network in relation to changes in depression and anxiety ratings. Fourteen patients, affected by chronic active C-hepatitis, were treated with IFNalpha (3-6 MUI s.c. three/six times a week for 6 months) and had measurements of serum IFN-gamma (IFNgamma), IL-2, IL-6, IL-6R, IL-8 and IL-10 before starting therapy and 2, 4, 16 and 24 weeks after immunotherapy with IFNalpha. Severity of depression and anxiety were measured with the Montgomery-Asberg Depression Rating Scale (MADRS) and the Hamilton Anxiety Rating Scale (HAM-A), respectively. Repeated measure (RM) design ANOVAs showed significantly higher MADRS and HAM-A scores 2-4 weeks and 4-6 months after starting IFNalpha-based immunotherapy than at baseline. RM design ANOVAs showed significantly higher serum IL-6 and IL-8 levels 2-4 weeks after starting IFNalpha-based immunotherapy and higher serum IL-10 levels 2-4 weeks and 4-6 months after starting therapy than at baseline. There were significant relationships between the IFNalpha-induced changes in serum IL-6 or IL-8 and the depression and anxiety scores. The findings show that IFNalpha-based immunotherapy induces the cytokine network and that IFNalpha-induced increases in IL-6 predicts the development of depressive symptoms. Depressive symptoms following IFNalpha treatment may be secondary to cytokine induction, including that of IL-6.
使用α干扰素（IFNα）进行免疫治疗时，若每日以3 - 10百万国际单位的剂量给药，每周两次或三次，持续至少1 - 3个月，可能会诱发抑郁症状、焦虑和重度抑郁症。此前研究表明，白细胞介素-2（IL-2）免疫治疗可显著诱导细胞因子网络，血清IL-6、IL-10和IL-2受体（IL-2R）水平升高可作为衡量指标，且免疫治疗诱导的细胞因子网络变化与抑郁评分增加显著相关。本研究的主要目的是研究IFNα免疫治疗对细胞因子网络的影响，以及与抑郁和焦虑评分变化的关系。14例慢性活动性丙型肝炎患者接受IFNα治疗（皮下注射3 - 6百万国际单位，每周三次/六次，共6个月），在开始治疗前以及IFNα免疫治疗后2、4、16和24周测量血清IFN-γ（IFNγ）、IL-2、IL-6、IL-6R、IL-8和IL-10。分别使用蒙哥马利-阿斯伯格抑郁评定量表（MADRS）和汉密尔顿焦虑评定量表（HAM-A）测量抑郁和焦虑的严重程度。重复测量（RM）设计方差分析显示，基于IFNα的免疫治疗开始后2 - 4周和4 - 6个月时，MADRS和HAM-A评分显著高于基线水平。RM设计方差分析显示，基于IFNα的免疫治疗开始后2 - 4周血清IL-6和IL-8水平显著升高，治疗开始后2 - 4周和4 - 6个月血清IL-10水平高于基线水平。IFNα诱导的血清IL-6或IL-8变化与抑郁和焦虑评分之间存在显著关系。研究结果表明，基于IFNα的免疫治疗可诱导细胞因子网络，且IFNα诱导的IL-6升高预示着抑郁症状的出现。IFNα治疗后的抑郁症状可能继发于细胞因子诱导，包括IL-6的诱导。
