Serum Levels Of IFN-γ Research Articles

Effects of Astragaloside IV on Hearing, Inflammatory Factors, and Intestinal Flora in Mice Exposed to Noise.

Long-term exposure to noise can cause irreversible hearing loss. Considering that there is no effective drug treatment, it is important to seek preventive treatment for noise-induced hearing loss (NIHL). Although astragaloside IV (AS-IV) protects against NIHL by reducing serum inflammatory factors, there is scarce information on the regulation of inflammatory factors by AS-IV to prevent NIHL. We investigated the hearing thresholds and relationship between the serum levels of inflammatory cytokines and intestinal microbiota of c57bl/6j mice exposed to noise (103 dB SPL 4 h·d-1) for 7 days, treated with or without AS-IV. Our results revealed a lower hearing threshold and lower serum levels of TNF-α, TNF-γ, IL-6, IL-1β, and IFN-γ in the mice treated with AS-IV. Additionally, AS-IV increased the abundance levels of the phylum Firmicutes, class Bacillus, order Lactobacillus, and family Lactobacillus (p < 0.05), and decreased those of the phylum Bacteroidetes and order Bacteroidales (p < 0.05). Lactobacillus and Bacilli negatively correlated with TNF-α, TNF-γ, and IL-1β; Erysipelotrichaceae negatively correlated with INF-γ; and Clostridiales positively correlated with IL-1β. In conclusion, AS-IV reduces the elevation of hearing thresholds in mice, preventing hearing loss in mice exposed to noise, and under the intervention of AS-IV, changes in the levels of inflammatory factors correlate with intestinal flora. We suggest that AS-IV improves intestinal flora and reduces inflammation levels in c57bl/6j mice exposed to noise.

T-bet+ B cells are activated by and control endogenous retroviruses through TLR-dependent mechanisms

Endogenous retroviruses (ERVs) are an integral part of the mammalian genome. The role of immune control of ERVs in general is poorly defined as is their function as anti-cancer immune targets or drivers of autoimmune disease. Here, we generate mouse-strains where Moloney-Murine Leukemia Virus tagged with GFP (ERV-GFP) infected the mouse germline. This enables us to analyze the role of genetic, epigenetic and cell intrinsic restriction factors in ERV activation and control. We identify an autoreactive B cell response against the neo-self/ERV antigen GFP as a key mechanism of ERV control. Hallmarks of this response are spontaneous ERV-GFP+ germinal center formation, elevated serum IFN-γ levels and a dependency on Age-associated B cells (ABCs) a subclass of T-bet+ memory B cells. Impairment of IgM B cell receptor-signal in nucleic-acid sensing TLR-deficient mice contributes to defective ERV control. Although ERVs are a part of the genome they break immune tolerance, induce immune surveillance against ERV-derived self-antigens and shape the host immune response.

Lactiplantibacillus plantarum and Saccharomyces cerevisiae-Fermented Coconut Water Alleviates Dextran Sodium Sulfate-Induced Enteritis in Wenchang Chicken: A Gut Microbiota and Metabolomic Approach.

In order to investigate the potential mechanisms of probiotic-fermented coconut water in treating enteritis, this study conducted a comprehensive analysis of the effects of probiotic intervention on the recovery from Dextran Sodium Sulfate-induced acute enteritis in Wenchang chicks. The analysis encompassed the assessment of growth performance, serum indicators, intestinal tissue structure, and metagenomic and metabolomic profiles of cecal contents in 60 Wenchang chicks subjected to intervention. This approach aimed to elucidate the impact of probiotic intervention on the recovery process from acute enteritis at both the genetic and metabolic levels in the avian model. The results revealed that intervention with Saccharomyces cerevisiae Y301 improved the growth rate of chicks. and intervention with Lactiplantibacillus plantarum MS2c regulated the glycerophospholipid metabolism pathway and reshaped the gut microbiota structure in modeling chicks with acute enteritis, reducing the abundance of potentially pathogenic bacteria from the Alistipes and increasing the abundance of potentially beneficial species from the Christensenellaceae. This intervention resulted in the production of specific gut metabolites, including Gentamicin C and polymyxin B2, recognized for their therapeutic effects on acute enteritis. The combined intervention of S. cerevisiae Y301 and L. plantarum MS2c not only enhanced growth performance but also mitigated intestinal wall damage and increased the abundance of gut metabolites such as gentamicin C and polymyxin B2, thereby mitigating symptoms of enteritis. Furthermore, this combined intervention reduced the levels of serum immune markers, including IL-10, IL-6, TNF-α, IFN-γ, and D-lactic acid, thus mitigating intestinal epithelial cell damage and promoting acute enteritis recovery. This study provides crucial insights into the mechanisms of action of probiotics and probiotic-fermented coconut water in acute enteritis recovery, offering new perspectives for sustainable farming practices for Wenchang chicken.

Proportion and Clinical Significance of γδT17/Th17/Tc17 Cells in Peripheral Blood of Uygur Patients with Chronic Lymphoblastic Leukemia

To explore the distribution of γδT17/Th17/Tc17 cells in the peripheral blood of Uygur patients with chronic lymphoblastic leukemia (CLL) and clinical significance. ELISA method was used to detect the levels of IL-17, IL-23, IL-6, and IFN-γ in the peripheral blood serum of 53 newly diagnosed Uygur patients with CLL and 30 healthy controls. Flow cytometry was used to determine the proportion of γδT/γδT17/Th17/Tc17 cells in the peripheral blood of Uygur CLL patients and controls, and the changes of the abover indexes in CLL Binet staging were observed. Compared with the control group, the proportion of γδT cells, γδT17 cells, and Th17 cells in the peripheral blood of Uygur CLL patients increased significantly （P <0.05）. γδT17 cell proportion in total lymphocytes was significantly higher than Th17 and Tc17 cell proportions（P <0.05）, and proportions of γδT, γδT17 cells increased gradually as the disease progressed. The levels of cytokines IL-17, IL-23, and IL-6 in peripheral blood of Uygur patients with CLL were significantly higher than those in the control group（P <0.05）, while the level of cytokine IFN-γ was significantly lower（P <0.05）. The level of IL-17 in peripheral blood decreased gradually as the disease progressed（P <0.05）. γδT and γδT17 are abnormally highly expressed in Uygur CLL , which are related to the stage of disease and participate in the occurrence and development of CLL.

Microwave ablation enhances the systemic immune response in patients with lung cancer.

Microwave ablation (MWA) is a key alternative therapy to conventional surgery for the treatment of lung cancer. In addition to eliminating local tumors, MWA may promote antitumor immunological responses, such as abscopal effects in distant lesions. However, the intensity of MWA is limited and the underlying mechanisms are not well-defined. The present study assessed the impact of MWA on immune cell subsets and cytokines in patients with lung cancer. A total of 45 patients with lung cancer who underwent percutaneous lung tumor MWA were enrolled. Peripheral blood samples were collected before and 24 h after MWA and changes in immune cell subsets [lymphocytes, CD3+, CD4+ and CD8+ T cells, B cells and natural killer (NK) cells] and serum cytokine levels (IL-1β, IL-2, IL-4-6, IL-8, IL-10, IL-12p70, IL-17A and F, IL-22, TNF-α, TNF-β and IFN-γ) were assessed by flow cytometry and ELISA. The number of total lymphocytes, CD4+ T and NK cells in the peripheral blood significantly decreased 24 h after MWA, while number of CD8+ T cells remained stable, leading to a higher proportion of CD8+ T cells. In addition, the serum levels of IL-2, IL-1β, IL-6, IL-12p70, IL-22, TNF-α and IFN-γ were significantly increased 24 h after MWA, indicating a T helper 1 type immune response. The immune response in patients with advanced stage disease was comparable with patients in the early stage group; however, the number of total lymphocytes and CD3+ T cells significantly decreased and the ratio of CD4/CD8 and IL-2 levels significantly increased. The early immune response after MWA may contribute to systemic antitumor immunity in patients with both early and advanced disease. Thus, MWA may exhibit potential as a local therapy and trigger abscopal effects in distant lesions in patients with lung cancer.

A novel bivalent inactivated vaccine for ducks against Riemerella anatipestifer based on serotype distribution in southern China

Riemerella anatipestifer (RA) causes epizootic infectious polyserositis in ducks with high mortality and leads to huge economic losses worldwide. Bacterial resistance poses a challenge for the control of the disease, vaccines failed to provide ideal cross-protection. Thus, the preparation of vaccines based on popular serotypes is important. In this study, we collected 700 brain and liver tissues of dead ducks from 8 provinces in southern China from 2016 to 2022 and obtained 195 RA isolates with serotypes 1, 2, 7, and 10. Serotypes 1 and 2 were the most prevalent (82%). A novel bivalent inactivated vaccine WZX-XT5 containing propolis adjuvant was prepared, we chose XT5 (serotype 1) and WZX (serotype 2) as vaccine strains and evaluated WZX-XT5-induced immune response and protective efficacy in ducks. Results showed that the XT5 (LD50, 3.5 × 103 CFU) exhibited high virulence and provided better protection against RA compared with ZXP, DCR and LCF1 (LD50, 108 CFU). Notably, the dose of 109 CFU provided ideal protection compared with 108 CFU, propolis and oil emulsion adjuvants induced stronger protective efficacy compared with aluminum hydroxide adjuvant. Importantly, WZX-XT5 immunization induced high levels of RA-specific IgY, IFN-γ, IL-2, and IL-4 in serum and offered over 90% protection against RA with ultra-high lethal dose in ducks. Additionally, no clinical signs of RA infection or obvious pathological damage in tissues were observed in protected ducks. Overall, this study first reports the identification, serotyping and virulence of RA in ducks of southern China and the preparation of a novel bivalent inactivated vaccine, providing useful scientific information to prevent and control RA infection.

Effect of BAFF blockade on the B cell receptor repertoire and transcriptome in a mouse model of systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease. Anti-B-cell-activating factor (BAFF) therapy effectively depletes B cells and reduces SLE disease activity. This research aimed to evaluate the effect of BAFF blockade on B cell receptor (BCR) repertoire and gene expression. Through next-generation sequencing, we analyzed gene expression and BCR repertoire in MRL/lpr mice that received long-term anti-BAFF therapy. Based on gene expression profiles, we predicted the relative proportion of immune cells using ImmuCellAI-mouse, validating our predictions via flow cytometry and FluoroSpot. The loss of BCR repertoire diversity and richness, along with increased clonality and differential frequency distribution of the immunoglobulin heavy chain variable (IGHV) segment gene usage, were observed in BAFF-blockade mice. Meanwhile, the distribution of complementarity-determining region 3 (CDR3) length and CDR3 amino acid usage remained unaffected. BAFF blockade resulted in extensive changes in gene expression, particularly that of genes related to B cells and immunoglobulins. Besides, the tumor necrosis factor (TNF)-α responses and interferon (IFN)-α/γ were downregulated, consistent with the decrease in IFN-γ and TNF-α serum levels following anti-BAFF therapy. In addition, BAFF blockade significantly reduced B cell subpopulations and plasmacytoid dendritic cells, and caused the depletion of antibody-secreting cells. Our comparative BCR repertoire and transcriptome analyses of MRL/lpr mice subjected to BAFF blockade provide innovative insights into the molecular pathophysiology of SLE.

Expressions of Type I-III Interferons in Sjögren's Syndrome and Non-Sjögren's Dry Eye.

Systemic implications create a critical need for identification of dry eye patients with Sjögren syndrome (SS). Herein, we aimed to determine expressions of type I-III interferons (IFNs) in dry eye patients with or without underlying SS and their differential diagnosis. A prospective, observational, case-control study was performed on 140 dry eye patients among which 78 patients were diagnosed with SS. Clinical evaluations included ELISA detections of serum type I IFN (IFN-α and IFN-β, type II IFN (IFN-γ), and type III IFN (IFN-λ1/IL-29, IFN-λ2/IL-28, and IFN-λ3/IL-28B), as well as reporter cell assay for serum type I IFN activity. The serum levels of IFN-α and IFN-β were notably higher in dry eye patients with SS than those without underlying SS (p &lt; 0.0001). The functional assay for serum type I IFN activity showed the mean summed scores in dry eye patients with SS were remarkably increased compared to those without underlying SS (p &lt; 0.0001). The serum levels of IFN-γ and IFN-λ1/IL-29 seemed higher in dry eye patients with SS than those without underlying SS (p &lt; 0.0001). The serum levels of type I IFN (IFN-α combined with IFN-β), type II IFN (IFN-γ level), and type III IFN (IFN-λ1/IL-29) used as a test to predict underlying SS among dry eye patients produced an area under the curve of 0.86, 0.73, and 0.94, respectively. Serum levels of type I-III IFNs, especially IFN-α, IFN-β, and IFN-λ1/IL-29, may serve as a useful biomarker for identification of SS dry eye from non-SS dry eye.

Elevated NS1 serum levels reduce CD119 expression and CXCL-10 synthesis in patients with dengue hemorrhagic fever.

The intensity of dengue virus (DV) replication and circulating non-structural protein 1 (NS1) levels may promote changes in the human immune response and favor severe forms of infection. We investigated the correlations between NS1 with CXCL-8, CXCL-10, IFN-γ, and IL-12p40 serum levels, and IFN-γ receptor α chain (CD119) expression, and CXCL10 production by peripheral blood mononuclear cells (PBMCs) stimulated with recombinant IFN-γ in DV-infected patients with different clinical forms. Dengue virus NS1, CXCL-8, CXCL-10, IFN-γ, and IL-12p40 serum levels were measured in 152 DV-infected patients with different clinical forms and 20 non-infected individuals (NI) using enzyme-linked immunosorbent assay (ELISA). In addition, we investigated the CXCL-10 production after in vitro IFN-γ stimulation of PBMCs from 48 DV-infected individuals (with different clinical forms of dengue fever) and 20 NI individuals using ELISA, and CD119 expression on CD14+ cells with flow cytometry. Patients with dengue hemorrhagic fever (DHF) had significantly higher NS1, CXCL-8, and CXCL-10 serum levels than those with classic dengue fever (DF). The response of PBMCs to IFN-γ stimulation was lower in patients with DHF than in those with DF or dengue with complications (DWC), with lower CD119 expression and reduced CXCL-10 synthesis. In addition, these alterations are associated with high NS1 serum levels. Patients with DHF reported high NS1 levels, low CD119 expression, and low CXCL-10 synthesis in PBMCs, which may be associated with infection progression and severity.

Influence of dietary and lifestyle factors on levels of inflammatory markers (IL-6, IFN-γ and TNF-α) in obese subjects.

The low-grade inflammation occurring in obese individuals leads to many diseases, including cardiovascular disease (CVD). Dietary patterns, food groups or nutrients in a well-balanced diet may reduce the level of pro-inflammatory markers and the risk of obesity-related morbidities. Our study aims to describe three cytokines in obese patients in relation to dietary habits, lifestyle and body composition. Serum samples were collected from 84 obese adult volunteer subjects [body mass index (BMI) ≥ 30 kg/m2] to analyze the concentrations of interleukin 6 (IL-6), tumor necrosis factor α (TNF-α) and interferon γ (IFN-γ). The subjects were tested by bioelectrical impedance analysis (BIA) and completed a three-day food diary and original questionnaire with the FFQ-6 food consumption frequency questionnaire. Higher serum levels of IL-6 and IFN-γ were found in patients with atherosclerosis, but the group was too small for a reliable correlation. Subcutaneous but not visceral adipose tissue correlated positively with IL-6 levels. Dietary factors such as amount of sugars, including galactose and sucrose, in the diet and the frequency of consumption of sweet flavored dairy products correlated positively with the levels of IL-6 and TNF-α, while the frequency of alcohol consumption negatively correlated with the level of IL-6. The greater the frequency of sports, the higher was the level of IL-6. In obese individuals, the level of pro-inflammatory cytokines could predispose to atherosclerosis and is associated with dietary factors and lifestyle.

High amniotic fluid fractalkine and MIP-1β levels are associated with intrauterine growth restriction: a prospective cohort study.

Proinflammatory chemokines have been shown to play crucial roles in implantation, spiral artery invasion, and the fetomaternal immunological response. In this context, we investigated the levels of fractalkine (CX3CL1) and chemokine CC motif ligand 4 (CCL4 or MIP-1β) in maternal serum and amniotic fluids in pregnant women with intrauterine growth restriction (IUGR). This prospective cohort study was carried out at Fırat University Obstetrics Clinic between January 1, 2022 and July 1, 2022. Group (G) 1: The control group consisted of 40 pregnant women who underwent elective cesarean section (CS) at 38-40 weeks of gestation. G2: A total of 40 pregnant women with IUGR at 28-37 weeks of gestation were included in the study group. Levels of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), interferon-gamma (IFN-γ), hypoxia-inducible factor-1 alpha (HIF-1α), macrophage inflammatory protein-1 beta (MIP-1β), and fractalkine were measured in maternal serum and amniotic fluid samples obtained during CS. When maternal age was compared, no statistically significant difference was observed between G1 and G2 (p = 0.374). The number of gravidity was found to be statistically higher in G1 compared to G2 (p = 0.003). The mean gestational week was statistically higher in G1 (p < 0.001). Maternal serum MIP-1β (p = 0.03) and IFN-γ (p = 0.006) levels were higher in G1. The birth weight of the baby (p < 0.001) and umbilical cord blood gas pH value (p < 0.001) at birth were higher in G1. HIF-1α (p < 0.001), fractalkine (p < 0.001), MIP-1β (p < 0.001), TNF-α (p = 0.007), IL-1β (p < 0.001), and IFN-γ levels (p = 0.007) in amniotic fluid were higher in G2. Elevated levels of proinflammatory factors, including fractalkine and MIP-1β, along with inflammatory factors such as TNF-α, IL-1β, and IFN-γ, as well as increased HIF-1α levels in amniotic fluid, are associated with intrauterine growth restriction (IUGR) attributed to a hypoxic amniotic environment.

Serum levels of IFN-γ and IL-4 in hospitalised COVID-19 patients – evidence of reduced cytokine storm in discharged patients

Introduction and aim. Coronavirus disease 2019 is characterised by cytokine storm and it was managed with repurposed drugs, however the effect of this treatment on cytokine storm is unknown. The aim of the study was to investigate the effect of repurposed management on serum Th1 pro-inflammation cytokine (IFN-γ) and Th2 anti-inflammation cytokine (IL-4) in COVID-19 patients. Material and methods. The levels of IFN-γ and IL-4 were determined in sera from 45 COVID-19 patients at admission followed-up till discharge after repurposed treatment using ELISA. The mean levels and proportions above normal reference ranges of IFN-γ and IL-4 were compared in COVID-19 at admission and discharge. Results. The mean values of IFN-γ and IL-4 were significantly higher in COVID-19 patients at admission compared with discharged COVID-19 patients whereas IFN-γ:IL-4 ratio was significantly higher in discharged COVID-19 patients compared with admitted COVID-19 patients. Significantly higher proportion of COVID-19 patients at discharge had IFN-γ within the normal reference ranges compared with COVID-19 patients at admission whereas the proportions of COVID-19 patients at discharge and COVID-19 patients at admission having IL-4 within the normal reference ranges were the same. Conclusion. Cytokine storm was evidenced in COVID-19 patients at admission and repurposed treatment suppressed pro-inflammation cytokine (IFN-γ) in most discharged COVID-19 patients.

Correlation of Serum Th1/Th2 Cytokines with Insulin Resistance in Gestational Diabetes Mellitus

Objective: To investigate the correlation between serum Th1/Th2 cytokines and insulin resistance in gestational diabetes mellitus (GDM). Methods: A total of 50 cases of pregnant women diagnosed with GDM and 50 healthy pregnant women who visited the Affiliated Hospital of Hebei University from January 2019 to December 2022 were recruited and divided into the GDM group and control group. Serum Th1/Th2 cytokines were observed and analyzed. Results: In the GDM group, serum IFN-γ levels were significantly higher than in the control group (P &lt; 0.01), while there was no statistically significant difference in IL-4 levels (P &gt; 0.05). Within the GDM group, HOMA-IR showed a positive correlation with IFN-γ (r = 0.67, P &lt; 0.01) and no correlation with IL-4 (r = 0.19, P &gt; 0.05). Within the control group, HOMA-IR did not correlate with either IFN-γ or IL-4 (r = 0.23, P &gt; 0.05; r = 0.15, P &gt; 0.05). Conclusion: The study concludes that the serum Th1 cytokine IFN-γ is correlated with insulin resistance in GDM, providing a novel perspective on the pathogenesis of GDM. Future studies should further explore the mechanisms and interventions to offer improved treatment options for patients with GDM.

Activated Tim-3/Galectin-9 participated in the development of multiple myeloma by negatively regulating CD4 T cells

ABSTRACT The interaction between Tim-3 on T cells and its ligand Galectin-9 negatively regulates the cellular immune response. However, the regulation of Tim-3/Galectin-9 on CD4 T cell subsets in multiple myeloma (MM) remains unclear. The aim of this study was to investigate the relationship between the regulation of CD4 T cell subsets by the Tim-3/Galectin-9 pathway and clinical prognostic indicators in MM. Tim-3/Galectin-9 were detected by flow cytometry, PCR and ELISA in 60 MM patients and 40 healthy controls, and its correlation with clinical prognostic parameters was analyzed. The expressions of Tim-3 on CD4 T cells, Galectin-9 mRNA in PBMC and level of Galectin-9 protein in serum were significantly elevated in MM patients, especially those with poor prognostic indicators. In MM patients, Tim-3 was highly expressed on the surfaces of Th1, Th2, and Th17 cells, but lowly expressed on Treg. Moreover, level of cytokine IFN-γ in serum was negatively correlated with Tim-3+Th1 cell and Galectin-9mRNA, Galectin-9 protein level. In addition, cell culture experiments showed that the anti-tumor effect and the ability to secrete IFN-γ were restored by blocking the Tim-3/Galectin-9 pathway. In MM patients, Tim-3/Galectin-9 is elevated and associated with disease progression, by inhibiting the cytotoxic function of Th1, and also promoting Th2 and Th17 to be involved in immune escape of MM. Therefore, Tim-3/Galectin-9 may serve as a new immunotherapeutic target for MM patients.

IL-10 and IFN-γ as markers for early recognition of pediatric systemic lupus erythematosus complicated with macrophage activation syndrome.

To compare the clinical and laboratory characteristics of pediatric-onset systemic lupus erythematosus (pSLE), pSLE with macrophage activation syndrome (MAS), and pSLE with recurrent MAS, and to find biomarkers for the differential diagnosis of these diseases. Demographic, clinical, laboratory and radiological data were analyzed for three groups of patients: 18 cases of pSLE with MAS, 48 age- and sex-matched cases of active pSLE without MAS and 40 age- and sex-matched cases of pSLE with inactive disease. One case of a 9-year-old girl with recurrent MAS as the primary manifestation of SLE also was recorded. IL-10 and IFN-γ levels were significantly higher in pSLE patients with MAS than in pSLE patients without MAS, and were significantly correlated with SLE and MAS laboratory features. Levels of IL-10 > 7.25 pg/ml had a high sensitivity and levels of IFN-γ > 6.7 pg/ml had a high specificity for predicting MAS in pSLE. Constitutional symptoms were evident in the case of recurrent MAS in pSLE, and traditional immunosuppressive therapies were unable to prevent the next MAS episode. Compared with pSLE and pSLE-MAS with a single episode, pSLE with recurrent MAS has different clinical manifestations and responses to treatment, requiring intensive studies to elucidate the underlying pathogenic mechanisms. Elevated serum levels of IL-10 and IFN-γ may be correlated with pSLE with MAS, and can serve as serum biomarkers for pSLE with MAS.

Association between Proinflammatory Cytokines and Lung Cancer Risk: A Case-Cohort Study from a Community-Based Prospective Cohort

Recent studies have shed light on alterations to the proinflammatory tumor microenvironment as a significant carcinogenic mechanism. Despite previous studies on associations between proinflammatory cytokines and lung cancer risk, few studies have been conducted in Asian populations. This study aimed to investigate associations between proinflammatory cytokines and lung cancer risk, considering histological types, in the Korean general population. We carried out a case-cohort study on the Korean National Cancer Center Community (KNCCC) cohort (lung cancer cases: 136, subcohort: 822). Pre-diagnostic serum levels of proinflammatory cytokines (i.e., IL-6, TNF-α, IL-1β, IFN-γ, and IL-10) were measured using Quantikine® ELISA. A Cox proportional-hazards regression analysis was conducted. In this study, serum levels of IL-6, IL-1β, and IFN-γ were associated with lung cancer risk. IL-6 was associated with lung cancer, regardless of the histological type. IL-1β had an association only with adenocarcinoma, while IFN-γ had an association only with squamous-cell carcinoma. This study shows associations between serum levels of IL-6, IL-1β, and IFN-γ and lung cancer risk, underscoring the potential of these cytokines to act as risk biomarkers. The utilization of these biomarkers for risk prediction may hold the promise of facilitating the identification of the high-risk population.

Significance of Tim-3 and Its Ligand Galectin-9 in Th1/Th2 Imbalance in Patients with Multiple Myeloma

To investigate the significance of Tim-3 and Galectin-9 in Th1/Th2 imbalance in patients with multiple myeloma (MM). 55 newly diagnosed MM patients and 20 healthy controls were included. Flow cytometry was used to detect the expression of Tim-3 on CD4+T cells, the proportion of Th1, Th2, Tim-3+Th1 and Tim-3+Th2 cells in peripheral blood. ELISA was used to detect the levels of cytokines IFN-γ and IL-4 in serum, and PCR was used to detect the level of Galectin-9 mRNA. Then the correlations between Galectin-9 mRNA expression and Th-cell subsets and related cytokine levels, as well as the relationship between Tim-3+Th1/Tim-3+Th2 ratio and corresponding clinical features were analyzed. Compared with the control group, the expression of Tim-3 on CD4+T cells in peripheral blood of MM patients was significantly increased (P<0.05), the proportions of Tim-3+Th1 cells, Tim-3+Th2 cells and Tim-3+Th1/Tim-3+Th2 ratio in MM patients were also increased (P<0.05), while the proportion of Th1 cells and Th1/Th2 ratio in MM patients were significantly decreased (P<0.05). The level of cytokine IFN-γ and IFN-γ/IL-4 ratio in MM patients were significantly decreased (P<0.05), while the level of cytokine IL-4 was increased (P<0.05). The mRNA levels of Galectin-9 in MM patients were significantly increased (P<0.05). The levels of Galectin-9 mRNA were positively correlated with Tim-3+CD4+T cells (r=0.663), Tim-3+Th2 cells (r=0.492) and IL-4 (r=0.470), while negatively correlated with IFN-γ (r=-0.593). The ratios of Tim-3+Th1/Tim-3+Th2 in MM patients were positively correlated with ISS stage (r=0.511), osteolytic damage (r=0.556) and chromosome abnormality (r=0.632). These results suggest that Tim-3 and Galectin-9 are involved in Th1/Th2 imbalance in MM patients, and the high ratio of Tim-3+Th1/Tim-3+Th2 is associated with poor clinical prognosis.

Combination of ketogenic diet and probiotics inhibits breast cancer in mice by immune system modulation and reduction of Insulin growth factor-1

Breast cancer (BC) is the most prevalent malignancy in women and the first tumor type in the world. Ketogenic diets (KD), which are high in fat, low in carbohydrates, and sufficient in protein, can be used alone or as adjuvants with cancer drug medication as cancer therapy or prevention methods. Probiotics are nonpathogenic microorganisms or groups of bacteria that live in the gut and nourish the host body. In this work, we tested a new KD-probiotic combination against breast cancer implanted in mice. Several combination of probiotics (1×109 CFU/0.5ml) and KD (14.1 kcal/2g) reduced tumor size and enhanced cure rate. KD and combination therapy groups increased beta-hydroxybutyrate (β-OHB) while decrease blood glucose, and IGF-1.IFN-γ, IL-2, IL-4, and IL-10 serum levels were measured to assess immune reaction to various therapies. Combination and probiotics therapy raised IFN-γ, and IL-4 levels, however IL-10 level did decrease in all treated group with highest decrease in combination group. In the safety profile, probiotics, ketogenic diet, and their combination were safe. Overall, the combination of a ketogenic diet and probiotics has the potential to be utilized in the future development of anti-cancer nutrition to augment conventional therapies. Graphical abstract. Summary of the effect of Ketogenic diet, Probiotics and its combination on EMP-6 breast cancer cell and in vivo:

Ursolic acid derivative UAOS-Na treats experimental autoimmune encephalomyelitis by immunoregulation and protecting myelin.

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). Ursolic acid (UA) can be used in the MS treatment with anti-inflammatory and neuroprotective activities. However, UA is insoluble in water, which may affect its medication effectiveness. In our previous study, UAOS-Na, a water-soluble derivative of UA was obtained. In this study, we evaluated the pharmacological effects and explored its underlying mechanism of UAOS-Na on experimental autoimmune encephalomyelitis (EAE). Firstly, the pharmacodynamics of UAOS-Na was investigated in EAE and Cuprizone-induced mice. And then the possible mechanisms were investigated by TMT proteomics and verified by in vitro and in vivo experiments. UAOS-Na (30 mg/kg/d) delayed the onset time of EAE from 11.78 days post immunization (dpi) to 14.33 dpi, reduced the incidence from 90.0% to 42.9%. UAOS-Na (60 mg/kg/d) reduced the serum levels of IFN-γ, IL-17A, TNF-α and IL-6, reduced the mononuclear cell infiltration of spinal cord, and inhibited the overexpression of key transcription factors T-bet and ROR-γt of EAE mouse spinal cord. In addition, UAOS-Na attenuated demyelination and astrogliosis in the CNS of EAE and cuprizone-induced mice. Mechanistically, proteomics showed that 96 differential expression proteins (DEPs) were enriched and 94 were upregulated in EAE mice compared with normal group. After UAOS-Na treatment, 16 DEPs were enriched and 15 were downregulated, and these DEPs were markedly enriched in antigen processing and presentation (APP) signaling pathway. Moreover, UAOS-Na downregulated the protein levels of Tapbp and H2-T23 in MHC-I antigen presentation pathway and reduced the proliferation of splenic CD8 T cells, thereby inhibiting the CNS infiltration of CD8 T cells. Our findings demonstrated that UAOS-Na has both myelin protective and anti-inflammatory effects. And it could reduce the inflammation of MS by downregulating the expression of Tapbp and H2-T23 in the MHC-I antigen presentation pathway.

Growth differentiation factor-15 is an IFN-γ regulated mediator of infection-induced weight loss and the hepatic FGF21 response

Infections are often accompanied by weight loss caused by alterations in host behavior and metabolism, also known as sickness behaviors. Recent studies have revealed that sickness behaviors can either promote or impede survival during infections depending on factors such as the type of infectious pathogen. Nevertheless, we have an incomplete understanding of the underlying mechanisms of sickness behaviors. Furthermore, although the host immune responses to infections have long been known to contribute to the induction of sickness behaviors, recent studies have identified emerging cytokines that are also key regulators of host metabolism during infection and inflammation, such as growth differentiation factor 15 (GDF-15). GDF-15 is a distant member of the TGF-β superfamily that causes weight loss by suppressing appetite and food consumption and causing emesis. These effects require activation of neurons that express the only known GDF-15 receptor, the GFRAL receptor. GDF-15 also functions in the periphery including the induction of ketogenesis and immunoregulation. Nevertheless, the functions and regulation of GDF-15 during live infections is not yet known. Murine infection with avirulent Toxoplasma gondii is an established model to understand infection-induced weight loss. Past studies have determined that acute T. gondii infection causes weight loss due to diminished food consumption and increased energy expenditure through unknown mechanisms. Additionally, our lab previously demonstrated that T. gondii causes upregulation in serum GDF-15 in an IFN-γ-dependent manner during the post-acute phase of the infection. In this study, we interrogated the in-vivo functions and immune regulation of GDF-15 during Toxoplasma gondii infection. First, we found that in wild-type mice, acute T. gondii infection caused a significant weight loss that is preceded by elevation of serum levels of IFN-γ and GDF-15. To determine whether IFN-γ regulates GDF-15, we neutralized IFN-γ on days 5 and 6 and measured GDF-15 on day 7 and found that serum but not tissue levels of GDF-15 decreased after IFN-γ neutralization. Additionally, exogenous IFN-γ was sufficient to elevate serum GDF-15 in the absence of infection. Next, we compared the outcomes of T. gondii infection between WT and Gdf15−/− mice. We observed that the weight trajectories were declining in WT mice while they were increasing in Gdf15−/−mice during the acute phase of the infection. This difference in trajectories extended throughout the chronic infection resulting to an overall weight loss relative to initial weights in WT mice but not Gdf15−/−mice. Then, we determined that GDF-15 is not essential for survival and immunoregulation during T. gondii infection. We also demonstrated that GDF-15 is required for the induction of FGF21, stress-induced cytokine with prominent roles in regulating host metabolism. Finally, we discovered a cytokine cascade IFN-γ-GDF-15-FGF21 that is likely involved in the regulation of host metabolism. Overall, our study provides evidence that IFN-γ contributes to the regulation of host metabolism during infection by inducing GDF-15 and FGF21. GDF-15 orchestrates changes in host metabolism that supports the host immune response in clearing the infection. These physiological alterations induce FGF21, which in turn, orchestrates the adaptive responses to the effects of GDF-15, which can be detrimental when protracted.