Ovarian cancer (OC) poses a significant global health challenge with high mortality rates, emphasizing the need for improved treatment strategies. The immune system\'s role in OC progression and treatment response is increasingly recognized, particularly regarding peripheral blood mononuclear cells (PBMCs) and cytokine production. This study aimed to investigate PBMC subpopulations (T and B lymphocytes, natural killer cells, monocytes) and cytokine production, specifically interleukin-1 beta (IL-1β), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-10 (IL-10), interleukin-12 (IL-12), and tumor necrosis factor alpha (TNFα), in monocytes of OC patients both preoperatively and during the early postoperative period. Thirteen OC patients and 23 controls were enrolled. Preoperatively, OC patients exhibited changes in PBMC subpopulations, including decreased cytotoxic T cells, increased M2 monocytes, and the disbalance of monocyte cytokine production. These alterations persisted after surgery with subtle additional changes observed in PBMC subpopulations and cytokine expression in monocytes. Considering the pivotal role of these altered cells and cytokines in OC progression, our findings suggest that OC patients experience an enhanced pro-tumorigenic environment, which persists into the early postoperative period. These findings highlight the impact of surgery on the complex interaction between the immune system and OC progression. Further investigation is needed to clarify the underlying mechanisms during this early postoperative period, which may hold potential for interventions aimed at improving OC management.

OBJECTIVE: To detect the expression changes of interleukin-10 (IL-10) and transforming growth factor-β1 (TGF-β1) during the development of deep vein thrombosis in mice, and to explore the application value of them in thrombus age estimation.
METHODS: The mice in the experimental group were subjected to ligation of inferior vena cava. The mice were sacrificed by excessive anesthesia at 1 d, 3 d, 5 d, 7 d, 10 d, 14 d and 21 d after ligation, respectively. The inferior vena cava segment with thrombosis was extracted below the ligation point. The mice in the control group were not ligated, and the inferior vena cava segment at the same position as the experimental group was extracted. The expression changes of IL-10 and TGF-β1 were detected by immunohistochemistry (IHC), Western blotting and real-time qPCR.
RESULTS: IHC results revealed that IL-10 was mainly expressed in monocytes in thrombosis and TGF-β1 was mainly expressed in monocytes and fibroblast-like cells in thrombosis. Western blotting and real-time qPCR showed that the relative expression levels of IL-10 and TGF-β1 in each experimental group were higher than those in the control group. The mRNA and protein levels of IL-10 reached the peak at 7 d and 10 d after ligation, respectively. The mRNA expression level at 7 d after ligation was 4.72±0.15 times that of the control group, and the protein expression level at 10 d after ligation was 7.15±0.28 times that of the control group. The mRNA and protein levels of TGF-β1 reached the peak at 10 d and 14 d after ligation, respectively. The mRNA expression level at 10 d after ligation was 2.58±0.14 times that of the control group, and the protein expression level at 14 d after ligation was 4.34±0.19 times that of the control group.
CONCLUSIONS: The expressions of IL-10 and TGF-β1 during the evolution of deep vein thrombosis present time-dependent sequential changes, and the expression levels of IL-10 and TGF-β1 can provide a reference basis for thrombus age estimation.
目的: 检测小鼠深静脉血栓发展过程中白细胞介素-10（interleukin-10，IL-10）和转化生长因子-β1（transforming growth factor-β1，TGF-β1）的表达变化，探讨其在血栓形成时间推断中的应用价值。方法: 对实验组小鼠建立下腔静脉结扎模型，分别于术后1 d、3 d、5 d、7 d、10 d、14 d、21 d过量麻醉处死小鼠，在结扎点的下方提取形成血栓的下腔静脉段。对照组小鼠不进行结扎，提取与实验组相同部位的正常下腔静脉段作为对照样本。应用免疫组织化学染色、蛋白质印迹法和real-time qPCR检测IL-10和TGF-β1在血栓形成期间的表达变化。结果: 免疫组织化学染色结果显示，IL-10主要表达于血栓中的单核细胞，TGF-β1主要表达于血栓中的单核细胞和成纤维样细胞。蛋白质印迹法以及real-time qPCR检测结果显示，各实验组IL-10和TGF-β1的表达水平均高于对照组。IL-10的mRNA及蛋白水平分别于术后7 d和10 d达到峰值，术后7 d的mRNA表达量是对照组的（4.72±0.15）倍，术后10 d的蛋白表达量是对照组的（7.15±0.28）倍。TGF-β1的mRNA及蛋白水平分别于术后10 d和14 d达到峰值，术后10 d的mRNA表达量是对照组的（2.58±0.14）倍，术后14 d的蛋白表达量是对照组的（4.34±0.19）倍。结论: 深静脉血栓演变期间IL-10和TGF-β1呈现时序性表达变化，IL-10和TGF-β1的表达水平可以为血栓形成时间推断提供参考依据。.

Interleukins serve as communicating molecules between cells, mediating key interactions in the tumor microenvironment (TME) between immune cells and non-immune cells. Interleukin-10 (IL-10), a multifunctional cytokine with multiple properties, has been extensively studied in various aspects of immunology and cancer biology. IL-10 is pleiotropic, promotes cytotoxicity, yet inhibits antitumor-responses. In recent years, the role of IL-10 in ovarian cancer (OC) progression and treatment has gained significant scientific attention, elucidating the signaling pathways triggered by IL-10 action. OC, the leading cause of gynecologic cancer-related deaths, is characterized by ascites, which hosts an intricate TME that is not responsive to treatment by immune checkpoint inhibition. IL-10, known for its immunosuppressive and anti-inflammatory properties, plays a complex role in OC progression, immune modulation, and therapeutic response and has a potential therapeutic property as a target and as an effector. As the literature of basic science research studying the role of IL-10 in the TME of OC scopes a few decades and some data is contrasting, it is important to review the literature and provide concise input derived from it. This review aims to provide a comprehensive overview of the current understanding of IL-10 in OC, highlighting its influence on tumor growth, immune evasion, and potential as a therapeutic target.

UNASSIGNED: Systemic Lupus Erythematosus (SLE) is a chronic autoimmune condition that affects multiple organs significantly impacts morbidity and mortality. The development of SLE is influenced by genetic predisposition and dysregulated immune response. Our objective was to investigate miR-21, IL-10, and PDCD4 expression in SLE patient plasma and analyze their correlations and potential diagnostic and prognostic values.
UNASSIGNED: The study included 100 healthy subjects, 50 newly diagnosed (ND), and 50 under-treatment (UT) SLE patients. The patients were observed for 24 weeks to track relapses. miR-21 and PDCD4 gene expression levels were measured using real-time RT-PCR, and IL-10 production was measured using ELISA.
UNASSIGNED: miR-21 and IL-10 expression levels were significantly greater in SLE patients than in healthy subjects, with the highest levels observed in ND patients. PDCD4 expression was also significantly greater in SLE patients than in subjects, with the highest levels observed in UT patients. ROC curve analyses and Cox-Mantel Log-rank tests indicated miR-21, PDCD4, and IL-10 as proper diagnostic and prognostic biomarkers for SLE. The study also revealed a significant positive correlation between miR-21 and PDCD4 and IL-10 levels in SLE patients.
UNASSIGNED: The studies suggest that dysregulation of miR-21, PDCD4, and IL-10 in patients with SLE may contribute to disease development and provides new diagnostic and prognostic markers. Additionally, the observed correlation between miR-21, PDCD4, and IL-10 levels in SLE patients signifies a potential interplay between these molecules.

UNASSIGNED: The role and regulation mechanisms of the interleukin-6 and 10 (IL6 and IL-10) serum levels and the interaction between CD4+ and CD8+ lymphocytes with SARS-COV-2 IgM and IgG in the context of COVID-19 infection are not fully understood.
UNASSIGNED: This study was conducted on 45 COVID-19 patients and 45 healthy individuals. The IL-6 and IL-10 promoter methylation, IL-6 and IL-10 gene expression, SARS-COV-2 IgM, and IgG antibodies and CD4+ and CD8+ lymphocytes were studied by qMSP-PCR, Real-time PCR, ELISA, and flow cytometry techniques, respectively.
UNASSIGNED: The male ratio and mean age of critically ill patients\' group were significantly higher in compared to controls (P< 0.05). IL-6 gene expression and serum levels were significantly increased in patients compared to controls (P=0.002, 0.001), but IL-6 promoter methylation was not significantly decreased in patients (P=0.835). The IL-10 promoter methylation and expression were not different between cases and controls (0.326, 0.455), but serum IL-10 levels were higher in patients (P< 0.001). The CD4+ and CD8+ lymphocytes decreased (P< 0.001) and mean SARS-COV-2 IgG increased (P=0.002) in the patients compared to controls.
UNASSIGNED: The COVID-19 disease result in severe complications in men and elderly. The serum levels of interleukin-6 and 10 increases in COVID-19 infection, and the gene expression of these two interleukins underlying in this increase. The serum levels of IL-6, IL-10 and SARS-COV-2 IgG as well as CD4+ and CD8+ lymphocyte counts should be investigated to monitor patients and predict the course of disease.

Appropriate regulation of the inflammatory response is essential for survival. Interleukin-10 (IL-10), a well-known anti-inflammatory cytokine, plays a major role in controlling inflammation. In addition to immune cells, we previously demonstrated that the IL-10 receptor (IL-10R1) is expressed in dorsal root ganglion sensory neurons. There is emerging evidence that these sensory neurons contribute to immunoregulation, and we hypothesized that IL-10 signaling in dorsal root ganglion (DRG) neurons facilitates the regulation of the inflammatory response. We showed that mice that lack IL-10R1 specifically on advillin-positive neurons have exaggerated blood nitric oxide levels, spinal microglia activation, and cytokine upregulation in the spinal cord, liver, and gut compared to wild-type (WT) counterparts in response to systemic lipopolysaccharide (LPS) injection. Lack of IL-10R1 in DRG and trigeminal ganglion (TG) neurons also increased circulating and DRG levels of proinflammatory C-C motif chemokine ligand 2 (CCL2). Interestingly, analysis of published scRNA-seq data revealed that Ccl2 and Il10ra are expressed by similar types of DRG neurons; nonpeptidergic P2X purinoceptor (P2X3R + ) neurons. In primary cultures of DRG neurons, we demonstrated that IL-10R1 inhibits the production of CCL2, but not that of the neuropeptides substance P and calcitonin-gene related peptide (CGRP). Furthermore, our data indicate that ablation of Transient receptor potential vanilloid (TRPV)1 + neurons does not impact the regulation of CCL2 production by IL-10. In conclusion, we showed that IL-10 binds to its receptor on sensory neurons to downregulate CCL2 and contribute to immunoregulation by reducing the attraction of immune cells by DRG neuron-derived CCL2. This is the first evidence that anti-inflammatory cytokines limit inflammation through direct binding to receptors on sensory neurons. Our data also add to the growing literature that sensory neurons have immunomodulatory functions.

OBJECTIVE: Asthma is the most prevalent respiratory disease, caused by chronic bronchial inflammation. Cytokines are known to play an important role in the pathophysiology of asthma. This study aimed to compare interleukin-4 (IL-4) and interleukin-10 (IL-10) gene polymorphisms between Iranian pediatric asthmatic patients and healthy controls and to investigate IL4 and IL10 gene variations in children with atopic and non-atopic asthma phenotypes.
METHODS: In this prospective case-control study, a total of 95 unrelated pediatric asthmatic patients were recruited according to the Global Initiative for Asthma (GINA) criteria. The control group comprised two subgroups of 538 and 491 healthy individuals, undergoing IL4 and IL10 polymorphism assessments, respectively. The IL4 -589C/T (rs2243250) and IL10 -592A/C (rs1800872) gene polymorphisms were evaluated using the tetra-primer amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) assay.
RESULTS: The findings indicated a significant difference in IL4 gene polymorphisms at position -589 between the asthmatic and healthy control groups. However, no significant difference was found in terms of IL10 gene polymorphisms, and they were not associated with atopy in the patients.
CONCLUSIONS: The IL4 -589C/T polymorphism (rs2243250) can be a risk factor for asthma susceptibility, whereas the IL10 -592A/C polymorphism (rs1800872) is not a risk factor in the Iranian pediatric population. The results also showed that these polymorphisms are not risk factors for atopy in asthmatic children.

Interleukin (IL)-10-producing B (B10) cells are generated in response to signals from the tumor microenvironment and promote tumor growth by interacting with B10 cells. We investigated the distributions of immune cells in peripheral blood and tumor tissue samples from patients with gastric cancer (GC).
Patients with GC who underwent radical gastrectomy in Seoul St. Mary\'s Hospital between August 2020 and May 2021 were enrolled in this study. Forty-two samples of peripheral blood were collected, and a pair of gastric mucosal samples (normal and cancerous mucosa; did not influence tumor diagnosis or staging) was collected from each patient after surgery. B10 cells in peripheral blood and cancer mucosa samples were investigated by flow cytometry and immunofluorescence. AGS cells, gastric cancer cell line, were cultured with IL-10 and measured cell death and cytokine secretion. Also, AGS cells were co-cultured with CD19 + B cells and measured cytokine secretion.
The population of B10 cells was significantly larger in the blood of patients with GC compared with controls. In confocal images of gastric mucosal tissues, cancerous mucosa contained more B10 cells than normal mucosa. The population of B10 cells in cancerous mucosa increased with cancer stage. When AGS cells were cultured under cell-death conditions, cellular necrosis was significantly decreased, and proliferation was increased, for 1 day after IL-10 stimulation. Tumor necrosis factor (TNF)-α, IL-8, IL-1β, and vascular endothelial growth factor secretion by cancer cells was significantly increased by coculture of AGS cells with GC-derived CD19+ B cells.
B cells may be one of the populations that promote carcinogenesis by inducing the production of inflammatory mediators, such as IL-10, in GC. Targeting B10 cells activity could improve the outcomes of antitumor immunotherapy. Video Abstract.

BACKGROUND: Metabolic dysregulation and excessive inflammation are implicated in the pathogenesis of the highly infectious disease of coronavirus disease 2019 (COVID-19), which is caused by a newly emerging coronavirus (i.e., severe acute respiratory syndrome-coronavirus 2; SARS-CoV-2). The adenosine 5\'-monophosphate-activated protein kinase (AMPK), an energy sensor regulating the metabolic pathways in diverse cells, exerts a regulatory role in the immune system. This study aims to examine the mRNA expression level of AMPK and the plasma levels of interleukin-6 (IL-6) and IL-10 cytokines in patients with different grades of COVID-19.
METHODS: Peripheral blood was collected from 60 patients with COVID-19 (Moderate, severe, and critical). The plasma levels of IL-6 and IL-10 were quantified by enzyme-linked immunosorbent assay (ELISA), and the mRNA expression level of AMPK was determined using real-time PCR.
RESULTS: The results showed that the plasma levels of IL-6 increased significantly in critical and severe patients compared to moderate cases of COVID-19 (P < 0.001). Moreover, IL-10 plasma concentrations were significantly higher in critical and severe cases than in moderate cases of COVID-19 (P < 0.01 and P < 0.05, respectively). Also, the gene expression of AMPK was meaningfully enhanced in critical patients relative to moderate and severe cases of COVID-19, in order (P < 0.001 and P < 0.01, respectively). There was a positive association between AMPK gene expression and plasma levels of IL-6 and IL-10 (P = 0.006, r = 0.348, P = 0.028, r = 0.283, respectively).
CONCLUSIONS: Increasing AMPK gene expression is likely a necessary effort of the immune system to inhibit inflammation in critical COVID-19. However, this effort seems to be inadequate, probably due to factors that induce inflammation, like erythrocyte sedimentation rate (ESR) and IL-6.

Liver metastases are associated with poor response to current pharmacological treatments, including immunotherapy. We describe a lentiviral vector (LV) platform to selectively engineer liver macrophages, including Kupffer cells and tumor-associated macrophages (TAMs), to deliver type I interferon (IFNα) to liver metastases. Gene-based IFNα delivery delays the growth of colorectal and pancreatic ductal adenocarcinoma liver metastases in mice. Response to IFNα is associated with TAM immune activation, enhanced MHC-II-restricted antigen presentation and reduced exhaustion of CD8+ T cells. Conversely, increased IL-10 signaling, expansion of Eomes CD4+ T cells, a cell type displaying features of type I regulatory T (Tr1) cells, and CTLA-4 expression are associated with resistance to therapy. Targeting regulatory T cell functions by combinatorial CTLA-4 immune checkpoint blockade and IFNα LV delivery expands tumor-reactive T cells, attaining complete response in most mice. These findings support a promising therapeutic strategy with feasible translation to patients with unmet medical need.