Ferencova Nikola, Visnovcova Zuzana, Ondrejka Igor, Funakova Dana, Hrtanek Igor, Kelcikova Simona, Tonhajzerova Ingrid
Biomedical Centre Martin, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovak Republic.
Psychiatric Clinic, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, University Hospital Martin, Martin, Slovak Republic.
J Inflamm Res. 2022 Oct 26;15:5959-5976. doi: 10.2147/JIR.S387588. eCollection 2022.
Nowadays, the role of two tightly interconnected systems, the inflammatory response system (IRS) and the compensatory immune response system (CIRS) in depression, is increasingly discussed. Various studies indicate pro-inflammatory activity in adolescent depression; however, there is an almost complete lack of findings about IRS and CIRS balance. Thus, we aimed to assess different IRS and CIRS indices, profiles, and IRS/CIRS ratios in drug-naïve MDD patients at adolescent age, with respect to sex.
One hundred MDD adolescents (40 boys, average age: 15.4±1.2 yrs.) and 60 controls (28 boys, average age: 15.3±1.5 yrs.) were examined. Evaluated parameters were 1. plasma levels of interleukin (IL)-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, interferon gamma, tumor necrosis factor alpha (TNF-α), soluble receptor of IL-6 (sIL-6R), soluble receptors of TNF-α (sTNF-R1, sTNF-R2); 2. profiles: IL-6 trans-signaling, M1 macrophage signaling, helper T lymphocytes (Th) 1 profile, regulatory T lymphocytes (Treg)+Th2, allIRS, and allCIRS; 3. IRS vs CIRS activity ratios: TNF-α/TNF-R1, TNF-α/TNF-R2, TNF-α/sTNF-Rs (ie sTNF-R1+sTNF-R2), Th1/Th2, Th1/Treg, Th1/Th2+Treg, M1/Th2, M1/Treg, M1/Treg+Th2, allIRS/allCIRS.
MDD patients showed increased IL-4, IL-10, TNF-α, sIL-6R, Treg+Th2, allIRS, allCIRS, and TNF-α/sTNF-Rs, and decreased Th1/Th2+Treg. MDD females showed increased IL-10 and TNF-α compared to control females. MDD males showed increased IL-4, IL-10, sIL-6R, Treg+Th2, and TNF-α/TNF-R1 compared to control males. Increased sTNF-R1 was found in MDD males compared to MDD females. Positive correlations were found between CDI score and sIL-6R and IL-10 in the total group and between CDI score and IL-10 in adolescent males.
Our study for the first time extensively evaluated IRS and CIRS interactions revealing enhanced pro-inflammatory TNF-α signaling and IL-6 trans-signaling in association with increased IL-10- and IL-4-mediated anti-inflammatory activity in first-episode depression at the adolescent age. Moreover, results reflect the sex-specific simultaneous activation of IRS and CIRS pathways in adolescent depression.
如今，炎症反应系统（IRS）和代偿性免疫反应系统（CIRS）这两个紧密相连的系统在抑郁症中的作用越来越受到关注。多项研究表明青少年抑郁症存在促炎活性；然而，关于IRS和CIRS平衡的研究结果几乎完全缺失。因此，我们旨在评估初发抑郁症青少年患者中不同的IRS和CIRS指标、特征以及IRS/CIRS比值，并探讨性别差异。
研究纳入了100名患有抑郁症的青少年（40名男孩，平均年龄：15.4±1.2岁）和60名对照者（28名男孩，平均年龄：15.3±1.5岁）。评估的参数包括：1. 血浆白细胞介素（IL）-1α、IL-1β、IL-2、IL-4、IL-6、IL-8、IL-10、γ干扰素、肿瘤坏死因子α（TNF-α）、IL-6可溶性受体（sIL-6R）、TNF-α可溶性受体（sTNF-R1、sTNF-R2）水平；2. 特征：IL-6转信号传导、M1巨噬细胞信号传导、辅助性T淋巴细胞（Th）1特征、调节性T淋巴细胞（Treg）+Th2、全IRS和全CIRS；3. IRS与CIRS活性比值：TNF-α/TNF-R1、TNF-α/TNF-R2、TNF-α/sTNF-Rs（即sTNF-R1 + sTNF-R2）、Th1/Th2、Th1/Treg、Th1/Th2 + Treg、M1/Th2、M1/Treg、M1/Treg + Th2、全IRS/全CIRS。
抑郁症患者的IL-4、IL-10、TNF-α、sIL-6R、Treg + Th2、全IRS、全CIRS以及TNF-α/sTNF-Rs水平升高，Th1/Th2 + Treg降低。与对照女性相比，抑郁症女性的IL-10和TNF-α水平升高。与对照男性相比，抑郁症男性的IL-4、IL-10、sIL-6R、Treg + Th2以及TNF-α/TNF-R1升高。与抑郁症女性相比，抑郁症男性的sTNF-R1升高。在总体人群中，CDI评分与sIL-6R和IL-10之间存在正相关，在青少年男性中，CDI评分与IL-10之间存在正相关。
我们的研究首次广泛评估了IRS和CIRS的相互作用，揭示了在青少年初发抑郁症中促炎的TNF-α信号传导和IL-6转信号传导增强，同时伴有IL-10和IL-4介导的抗炎活性增加。此外，研究结果反映了青少年抑郁症中IRS和CIRS途径的性别特异性同时激活。
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