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Objective: Accumulating evidence supports the idea that inflammation may contribute to the pathophysiology of major depressive disorder (MDD). Duloxetine, a serotonin-norepinephrine reuptake inhibitor, exhibits anti-inflammatory effects both in vitro and in vivo. In this study, we investigated the impact of duloxetine on changes in serum proinflammatory cytokine levels among individuals diagnosed with MDD., Methods: A cohort of 23 drug-naïve individuals diagnosed with MDD and 23 healthy controls were included in this study. The severity of depressive symptoms was evaluated using the 24-item Hamilton Depression Scale (HAMD-24). A panel of 7 proinflammatory cytokines, including interleukin-1β (IL-1β), IL-2, IL-6, IL-8, IL-12, tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ), were quantified using multiplex Luminex assays. The levels of serum cytokines in healthy controls and patients with MDD were compared at baseline. All patients received duloxetine at a dosage range of 40-60 mg/day for a duration of 4 weeks. The HAMD-24 scores and serum cytokine levels were compared before and after duloxetine treatment., Results: Compared with healthy controls, patients with MDD had significantly greater levels of IL-2, IL-6, IL-8, IL-12, TNF-α, and IFN-γ (P < 0.05). Moreover, there was a significant decrease in HAMD-24 scores observed pre- and post-treatment (t = 13.161, P < 0.001). Furthermore, after 4 weeks of treatment, the serum levels of IL-8 (t = 3.605, P = 0.002), IL-12 (t = 2.559, P = 0.018), and IFN-γ (t = 3.567, P = 0.002) decreased significantly. However, there were no significant differences in other cytokines, including IL-1β, IL-2, IL-6, and TNF-α, before and after treatment (P > 0.05)., Conclusions: These findings present compelling evidence, potentially for the first time, indicating that duloxetine treatment may effectively reduce the serum concentrations of IL-8, IL-12, and IFN-γ in individuals diagnosed with MDD. However, the precise mechanisms underlying this effect remain unclear and warrant further investigation., (© 2024. The Author(s).)

Objective: Abnormal levels of blood cytokines have been demonstrated to be associated with both excess weight and major depressive disorder (MDD). However, few studies have addressed the direct effect of body mass index (BMI) on basal serum cytokines in individuals with first-episode drug-naïve MDD., Methods: A total of 49 patients with first-episode drug-naïve MDD were categorized into normal weight (18.5 ≤ BMI < 25 kg/m 2 ) and overweight (25 ≤ BMI < 30 kg/m 2 ) groups according to WHO-criteria. The severity of depressive symptoms was assessed using the 24-items Hamilton Depression Scale (HAMD-24). A total of 37 cytokines were measured using Multiplex Luminex Assays. The scores of HAMD-24 and the levels of serum cytokines between normal weight group and overweight group were compared. Multiple linear regression analysis was performed to evaluate the association between abnormal serum cytokines levels and group after adjusting for HAMD-24 scores. The correlation between BMI and the scores of HAMD-24 and the levels of serum cytokines was evaluated using Pearson correlation analysis., Results: The scores of HAMD-24 in overweight group were significantly higher than normal weight group ( t = -2.930, P = 0.005). Moreover, the levels of IL-1α, IL-1RA, IL-3, CXCL10, TNF-α, and ICAM-1 in overweight patients with MDD were significantly higher than those in normal-weight patients with MDD (all P < 0.05). Furthermore, after adjustment for HAMD-24 scores, there was a significant correlation between abnormal serum cytokines levels (IL-1α, IL-1RA, IL-3, CXCL10, TNF-α, and ICAM-1) and group (all P < 0.05). Additionally, BMI was positively correlated to the serum levels of IL-1α ( r = 0.428, P = 0.002), IL-3 ( r = 0.529, P < 0.001), IL-6 ( r = 0.285, P = 0.050), IL-10 ( r = 0.423, P = 0.003), IL-12 ( r = 0.367, P = 0.010), IL-15 ( r = 0.300, P = 0.036), CXCL10 ( r = 0.316, P = 0.030), TNF-α ( r = 0.338, P = 0.021), and ICAM-1 ( r = 0.440, P = 0.002) in MDD patients., Conclusions: These results provide direct evidence, probably for the first time, that overweight may be associated with several serum cytokines in patients with first-episode drug-naïve MDD. The underlying mechanisms are unclear and require further investigation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gao, Xu, Liang, Sun, Zhang, Shan, Ge and Xia.)

• Cytokines may be used as diagnostic biomarkers in discriminating MDD patients. • Positive relationship was found between TNF-α and HAMD-24 scores in MDD patients. • A combined panelset of IL-1α, IL-5, and ICAM-1 at baseline achieved a high accuracy in discriminating antidepressant nonresponders from responders. Several lines of evidence have suggested that cytokines are implicated in the pathophysiology of depression and antidepressant treatment outcome. However, the results are not always congruent and partly contradictory. We therefore examined the serum levels of multiple cytokines in patients with major depressive disorder (MDD), with the aim to identify serum cytokines-based biomarkers for MDD diagnosis and antidepressant response. Fifty-nine patients with MDD and 61 healthy controls were included. The baseline levels of serum cytokines between MDD group and control group were compared, and the discriminative ability of different cytokines in predicting MDD patients from healthy controls was investigated using the receiver operating characteristic (ROC) curve method. The baseline levels of serum cytokines between antidepressant nonresponders and responders were compared, and the discriminative ability of different cytokines in predicting nonresponders from responders was evaluated using the ROC curve method. Compared to controls, 15 of the 37 serum cytokines were increased, while 8 cytokines were decreased in MDD patients (all P < 0.05). The results of ROC curve showed that the Area Under Curve (AUC) values of 15 cytokines including IL-2, IL-5, IL-6, IL-8, IL-12, IL-13, IL-16, CCL3, CCL4, CCL17, CXCL10, TNF-α, TNF-β, VEGF-C, and FGF basic were greater than 0.7 in discriminating MDD patients from healthy control. Moreover, after 4-week treatment, levels of the 2 cytokines (IL-12 and TSLP) elevated at baseline significantly down-regulated, and levels of the 6 cytokines (IL-5, IL-16, CCL17, CXCL10, TNF-β, and PIGF) decreased at baseline significantly up-regulated (all P < 0.05). Furthermore, a positive relationship was found between TNF-α levels and Hamilton Depression Rating Scale-24 (HAMD-24) scores in patients with MDD at baseline (r = 0.302, P = 0.019). Additionally, compared to responders, nonresponders exhibited decreased levels of IL-1α, IL-5, IL-13, IL-15, VEGF, and ICAM-1 (all P < 0.05). The ROC curve analysis demonstrated that a combined panel of IL-1α, IL-5, and ICAM-1 achieved a high accuracy in discriminating antidepressant nonresponders from responders (AUC = 0.850, sensitivity = 83.3%, specificity = 81.8%). These results suggested that alterations in peripheral cytokines levels hold significant promise as biomarkers for MDD diagnosis and antidepressant response. [ABSTRACT FROM AUTHOR]

Psoriasis is a cutaneous disease mainly characterized by keratinocyte hyperproliferation, abnormal epidermal differentiation, inflammation and angiogenesis. In this study, we aimed to report the therapeutic potential of Diosgenin on psoriasis-like models and explore the underlying mechanisms. For in vitro studies, we initially evaluated the bioeffects of Diosgenin on keratinocytes by detecting the cell viability, cell cycle and apoptosis in HaCaT cells. To mimic psoriatic conditions, we established hyperproliferative model by stimulating HaCaT cells with LPS/IL-22 and inflammatory model by LPS/TNF-α stimulation. Meanwhile, differentiation in HaCaT cells and angiogenesis in HUVECs/HMEC-1 were observed. The influence of Diosgenin on above-mentioned conditions was examined. For in vivo studies, we dosed imiquimod (IMQ) -induced mice with Diosgenin and conducted hematoxylin-eosin (HE), TUNEL assay and immunohistochemistry (IHC) to evaluate histological changes, apoptosis and the status of keratinocyte proliferation, epidermal differentiation, vascularity and cutaneous inflammatory cell infiltration respectively. Results showed that Diosgenin inhibited HaCaT cell growth through cell cycle arrest and NFκB inhibition while induced apoptosis by regulating Caspase3, Bax and Bcl-2 protein expression. After Diosgenin treatment, NFκB nuclear translocation and IL-22 receptor dependent pathways were suppressed in LPS/IL-22 induced HaCaT cells respectively. Furthermore, Diosgenin downregulated proinflammatory cytokines through TLR4/Myd88 inhibition and upregulated several differentiation markers' expression in HaCaT cells. Additionally, Diosgenin inhibited vascular formation partially by reducing the VEGF-α expression in keratinocytes. In animal studies, Diosgenin attenuated psoriatic lesions on mice accordingly. This study suggests that Diosgenin might be a promising candidate for developing anti-psoriatic agents. [ABSTRACT FROM AUTHOR]