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Inflammation significantly impacts Parkinson's disease (PD), yet the intricate relationship between inflammatory markers and PD remains elusive. To identify the peripheral biomarkers of PD and its correlation with the motor and non-motor symptoms of PD. 79 PD patients and 65 controls were included in this study. Clinical information and the serum levels of IL-8, IL-27, IL-33, β-NGF, AgRP, and TRAILR2 in the participants were collected. Appropriate scales were used to assess the symptoms of PD. For the factors with significant differences in the two groups, multivariable logistic regression was used to determine its relationship with PD. Moreover, spearman correlation was conducted to explore the correlation between the factors and PD related symptoms. The IL-27 level was compared between the cognitively healthy PD group and the mild cognitive impairment in PD (PD-MCI). The serum level of TRAILR2 was positively correlated with age and was not associated with other clinical characteristics related to PD. Compared to controls, the serum levels of IL-27(P = 0.013) were increased whereas the levels of TRAILR2(P = 0.008) were decreased in PD patients. IL-8, IL-33, β-NGF, and AgRP showed no significant differences between the two groups. After controlling for the other variables, IL-27 was considered as an independent risk factor for PD in the multivariable logistic regression model. The receiver operating characteristic (ROC) curve for diagnosing PD with IL-27 yielded an area under the curve (AUC) of 0.621. Additionally, IL-27 level in PD patients was positively correlated with age, the disease duration, LEDD and negatively correlated with the MoCA scores. However, no significant difference was found in IL-27 levels between cognitively healthy PD and PD-MCI groups. Elevated serum IL-27 was a risk factor for PD and positively correlated with the cognitive decline in PD. Show less

Psoriasis and inflammatory bowel disease (IBD) are chronic immune-mediated diseases that adversely affect patients' quality of life. Interleukin (IL)-27 plays an important role in a variety of infectious diseases, autoimmune disorders, and cancers. However, its therapeutic effects in psoriasis and colitis remain underexplored. In this study, we evaluated the therapeutic potential of recombinant Lactococcus lactis (L. lactis) expressing IL-27 (pIL-27) in imiquimod-induced psoriasis and dextran sodium sulfate-induced colitis mouse models. In the psoriasis mouse model, oral administration of pIL-27 significantly reduced skin scaling, mitigated weight loss, lowered psoriasis area and severity index scores, diminished epidermal hyperplasia and inflammatory cell infiltration, and decreased inflammatory cytokine levels. In the colitis mouse model, oral administration of pIL-27 alleviated weight loss, improved disease activity index scores, prevented colon shortening, ameliorated histopathological changes, and decreased inflammatory cytokine levels. Furthermore, recombinant L. lactis expressing IL-27 could modulate the gut microbiota, increasing the amount of beneficial bacteria and reducing harmful bacteria in the intestine, thereby alleviating the progression of psoriasis and colitis. These results suggest the potential of IL-27 as a therapeutic option for treating psoriasis and IBD. Show less

Pregnancy is a risk factor for increased severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other respiratory infections, but the mechanisms underlying this risk are poorly understood. To gain insight into the role of pregnancy in modulating immune responses at baseline and upon SARS-CoV-2 infection, we collected peripheral blood mononuclear cells and plasma from 226 women, including 152 pregnant individuals and 74 non-pregnant women. We find that SARS-CoV-2 infection is associated with altered T cell responses in pregnant women, including a clonal expansion of CD4-expressing CD8 Show less

Interleukin-27 (IL-27), a potential mediator linking obesity to inflammatory diseases, is considered an important candidate for regulating obesity. The present study evaluated the relationship of IL-27 with obesity and insulin resistance (IR) and further investigated the changes in IL-27 levels after weight loss. The study analyzed 405 participants, of whom 62 with overweight or obesity completed one year of lifestyle intervention. The body compositions, including percent of body fat (PBF), visceral fat area (VFA), skeletal muscle mass (SMM), and visceral fat area to skeletal muscle mass ratio (VSR), were assessed using the bioelectrical impedance analysis method. Serum IL-27 levels were measured using the enzyme-linked immunosorbent assay (ELISA). IL-27 levels increased significantly with the increase in body mass index (BMI) (P < 0.001). Moreover, IL-27 levels were positively correlated with PBF, VFA, and VSR. Homeostatic model assessment for insulin resistance (HOMA-IR), the inverse of hepatic insulin sensitivity (1/HISI), adipose tissue insulin resistance (Adipo-IR), and homeostasis model assessment-adiponectin (HOMA-AD) increased significantly with each quartile of IL-27 levels (all P < 0.001). IL-27 levels significantly decreased after weight loss (P < 0.001). IL-27 was positively correlated with obesity, HOMA-IR, 1/HISI, Adipo-IR, and HOMA-AD. IL-27 levels significantly decreased after weight loss. Show less

Polycystic ovary syndrome (PCOS) is a common metabolic/ endocrine disorder seen predominantly in women in their reproductive age, which increases the risk of infertility, endometrial cancer and metabolic disorders. IL-27 and IL-38 are recently discovered, novel anti-inflammatory cytokines whose role in immune-endocrine dysfunction seen in PCOS is largely unknown. In the present study, we quantified these two cytokines along with markers for meta-inflammation (TNF-α, IL-6, IL-1β, IL-1Ra, IL-10 and TGF-β) and hormonal dysregulation (insulin, leptin, adiponectin, FGF-21, testosterone and DHEA-S) in the serum of PCOS women (n=44), along with age matched controls (n=20), by ELISA. We quantified serum lipid peroxidation, protein peroxidation, and nitrite levels using spectrophotometry. PCOS women had significantly elevated levels of IL-27, IL-38 along with TNF-α, IL-6, IL-1Ra, IL-10, FGF-21 and adiponectin, and decreased levels of TGF-β, SDF-1 and leptin. While there is no significant difference with respect to redox markers, nitrite levels were significantly increased in PCOS cases. The increased circulating levels of anti-inflammatory cytokines IL-27 and IL-38 under PCOS conditions warrant further investigation. To the best of our knowledge, this is the first report on IL-38 levels in PCOS. Show less

Psoriasis is characterized by accelerated proliferation of epidermal keratinocytes. IL-27 is relevant to psoriasis pathogenesis. We previously found that IL-27 stimulates the proliferation of keratinocytes. However, the mRNAs involved in the process have not been fully studied. This study aims to identify potential pathways and hub genes associated with proliferation in keratinocytes with IL-27 intervention by bioinformatics analysis. The mRNA expression profiles from HaCaT cells with or without IL-27 treated were analyzed by bioinformatics tools. The protein-protein interaction (PPI) network was constructed to screen gene clusters and hub genes associated with proliferation. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were used to identify the function of the mRNAs. The GEO database and quantitative real-time PCR (qPCR) were used to verify the expression levels of hub genes in psoriatic skin lesions and IL-27-treated psoriasiform keratinocytes, respectively. We found 1257 differentially expressed genes and screened 2 crucial gene clusters. GO analysis revealed that Cluster 1 was mainly enriched in "Mitotic sister chromatid segregation" and "Spindle". Cluster 2 was mainly enriched in the "Pyruvate metabolic process" and "Oxidoreductase complex". KEGG analysis showed that Cluster 1 and Cluster 2 were mainly enriched in "Cell cycle" and "Glycolysis/Gluconeogenesis", respectively. We then identified 6 hub genes enriched in the two pathways, including IL-27 possibly promotes glycolysis, mitochondrial oxidative phosphorylation, and cell cycle progression in keratinocytes. Additionally, we identified Show less

To evaluate the efficacy of subcutaneous specific immunotherapy (SCIT) for allergic rhinitis (AR) combined with asthma. A retrospective analysis of clinical data from 93 patients with AR combined with asthma admitted to our hospital from January 2022 to January 2023 was conducted. Based on the treatment interventions received, the patients were divided into a control group (n=46, receiving sublingual specific immunotherapy [SLIT]) and an observation group (n=47, receiving SCIT). Clinical treatment response, lung function, levels of immune indicators, levels of inflammatory indicators, and occurrence of adverse reactions were compared between the two groups. The total response rate was 95.74% in the observation group and 84.78% in the control group (P > 0.05). In terms of scores for symptom assessment, Total Nasal Symptom Score (TNSS), Depression Anxiety Stress Scale (DASS), and Nasal Allergy Symptom Score (NASS) scores in both groups decreased after treatment, with greater decreases in the observation group (P < 0.05). In addition, lung function was improved in both groups after treatment as reflected by increased Forced Expiratory Volume in one second to Forced Vital Capacity ratio (FEV1/FVC) and Peak Expiratory Flow (PEF) levels, with greater increases found in the observation group (P < 0.05). Among the immune and inflammatory indicators, Cluster of Differentiation 14 (CD14) and Interleukin-33 (IL-33) levels decreased, while Secretory Protein D-1 (SPD-1), serum Immunoglobulin G4 (sIgG4), Interferon-γ (INF-γ), and Interleukin-27 (IL-27) levels increased in both groups after treatment, with greater changes observed in the observation group (P < 0.05). There was no significant difference in the incidence of adverse reactions between the observation group (14.89%) and the control group (21.74%) (P > 0.05). In the treatment of AR combined with asthma, SCIT can better alleviate clinical symptoms, improve lung function, regulate immune and inflammatory responses in patients, and does not increase the risk of adverse reactions compared to SLIT. Show less

To explore the correlation between serum interleukin-22 (IL-22) and interleukin-27 (IL-27) levels and vasculopathy in patients with diabetic nephropathy (DN). A total of 104 DN patients treated at the Shanxi University of Traditional Chinese Medicine Affiliated Hospital were selected as the observation group, with another 104 healthy individuals, serving as the control group in this retrospective study. The baseline data and the serum levels of IL-22 and IL-27 were compared between the two groups. The observation group was divided into three subgroups based on their urinary albumin excretion rate (UAER): clinical albuminuria group (microangiopathy, 29 patients), microalbuminuria group (51 patients), and normal albuminuria group (24 patients). Logistic regression was used to analyze the factors influencing the occurrence of microangiopathy. According to whether they had major adverse cardiovascular events (MACE) during 6-month follow-up, the DN patients were divided into a MACE group (n = 39) and a non-MACE group (n = 65). The serum levels of IL-22 and IL-27 were then compared between the two groups. The clinical utility of IL-22 and IL-27 in the assessment of microangiopathy and prognosis was evaluated through receiver operating characteristic (ROC) curve analysis. Compared to the control group, the observation group exhibited significantly higher serum levels of fasting blood glucose, glycated hemoglobin, total cholesterol, triglycerides, low-density lipoprotein, uric acid, blood creatinine, cystatin C, IL-22 and IL-27, but lower glomerular filtration rate (all P<0.05). There were significant differences among different albuminuria groups in terms of duration of disease, serum levels of fasting blood glucose, low-density lipoprotein, cystatin C, IL-22, IL-27, and glomerular filtration rate (all P<0.05). Correlation analysis showed that the serum levels of IL-22 and IL-27 were positively correlated with the duration of disease and serum levels of fasting blood glucose, low-density lipoprotein, uric acid, blood creatinine and cystatin C. However, they were negatively correlated with glomerular filtration rate (P<0.05). The logistic regression analysis indicated that the glomerular filtration rate and serum levels of cystatin C, IL-22, and IL-27 were independent risk factors for the occurrence of microangiopathy. Compared to non-MACE group, the MACE group presented with higher serum IL-22 and IL-27 levels. ROC curve analysis showed that the AUC (Area Under the Curve) for combined detection (>0.9) of serum IL-22 and IL-27 levels was higher than that (>0.8) for each alone in assessing microangiopathy in DN patients. Additionally, the AUC for using serum IL-22 and IL-27 levels, whether individually or in combination, exceeded 0.7 when evaluating patient prognosis. Elevated serum IL-22 and IL-27 levels are closely associated with the severity of the DN and can serve as auxiliary indicators for assessing microangiopathy and prognosis in DN patients. Show less

The metabolic reprogramming of macrophages is a potential therapeutic strategy for sepsis treatment, but the mechanism underlying this reprogramming remains unclear. Since glycolysis can drive macrophage phenotype switching, the rate-limiting enzymes in glycolysis may be key to treating sepsis. Here, we found that, compared with other isoenzymes, the expression of 6-phosphofructokinase, muscle type (PFKM) was the most upregulated in monocytes from septic patients. Recombinant thrombomodulin (rTM) treatment downregulated the protein expression of PFKM in macrophages. Both rTM treatment and Pfkm knockout protected mice from sepsis and reduced the production of the proinflammatory cytokines IL-1β, IL-6, TNF-α, and IL-27, whereas PFKM overexpression increased the production of these cytokines. Mechanistically, rTM treatment inhibited glycolysis in macrophages by decreasing PFKM expression in a hypoxia-inducible factor-1α (HIF-1α)-dependent manner. HIF-1α overexpression increased methyltransferase-like 3 (METTL3) expression, elevated the m Show less

Tumor regression following immune checkpoint blockade (ICB) is often associated with immune-related adverse events (irAEs), marked by inflammation in non-cancerous tissues. This study was undertaken to investigate the functional relationship between anti-tumor and anti-self immunity, to facilitate irAE management while promoting anti-tumor immunity. Multiple biopsies from tumor and inflamed tissues were collected from a patient with melanoma experiencing both tumor regression and irAEs on ICB, who underwent rapid autopsy. Immune cells infiltrating melanoma lesions and inflamed normal tissues were subjected to gene expression profiling with multiplex qRT-PCR for 122 candidate genes. Subsequently, immunohistochemistry was conducted to assess the expression of 14 candidate markers of immune cell subsets and checkpoints. TCR-beta sequencing was used to explore T cell clonal repertoires across specimens. While genes involved in MHC I/II antigen presentation, IFN signaling, innate immunity and immunosuppression were abundantly expressed across specimens, irAE tissues over-expressed certain genes associated with immunosuppression (CSF1R, IL10RA, IL27/EBI3, FOXP3, KLRG1, SOCS1, TGFB1), including those in the COX-2/PGE2 pathway (IL1B, PTGER1/EP1 and PTGER4/EP4). Immunohistochemistry revealed similar proportions of immunosuppressive cell subsets and checkpoint molecules across samples. TCRseq did not indicate common TCR repertoires across tumor and inflammation sites, arguing against shared antigen recognition between anti-tumor and anti-self immunity in this patient. This comprehensive study of a single patient with melanoma experiencing both tumor regression and irAEs on ICB explores the immune landscape across these tissues, revealing similarities between anti-tumor and anti-self immunity. Further, it highlights expression of the COX-2/PGE2 pathway, which is known to be immunosuppressive and potentially mediates ICB resistance. Ongoing clinical trials of COX-2/PGE2 pathway inhibitors targeting the major COX-2 inducer IL-1B, COX-2 itself, or the PGE2 receptors EP2 and EP4 present new opportunities to promote anti-tumor activity, but may also have the potential to enhance the severity of ICB-induced irAEs. Show less

The most common central nervous system (CNS) inflammatory disease is multiple sclerosis (MS), modeled using experimental autoimmune encephalomyelitis (EAE). Mesenchymal stem cells (MSCs) exhibit potent immunomodulatory capabilities, including the suppression of immune cell functions and anti-inflammatory cytokine production. Female C57BL/6 mice (8-10 weeks old) were divided into three groups: 1. Control, 2. Allogeneic MSCs (ALO) treatment, and 3. Syngeneic MSCs (SYN) treatment. To induce EAE, myelin oligodendrocyte glycoprotein was injected subcutaneously with complete Freund's adjuvant, followed by intraperitoneal pertussis toxin. On Days 6 and 12 postimmunization, the treatment groups received intraperitoneal injections of 2 × 10 Show less

Patients with metastatic ovarian cancer (OvCa) have a 5-year survival rate of <30% due to the persisting dissemination of chemoresistant cells in the peritoneal fluid and the immunosuppressive microenvironment in the peritoneal cavity. Here, we report that intraperitoneal administration of β-glucan and IFNγ (BI) induced robust tumor regression in clinically relevant models of metastatic OvCa. BI induced tumor regression by controlling fluid tumor burden and activating localized antitumor immunity. β-glucan alone cleared ascites and eliminated fluid tumor cells by inducing intraperitoneal clotting in the fluid and Dectin-1-Syk-dependent NETosis in the omentum. In omentum tumors, BI expanded a novel subset of immunostimulatory IL27+ macrophages and neutralizing IL27 impaired BI efficacy in vivo. Moreover, BI directly induced IL27 secretion in macrophages where single agent treatment did not. Finally, BI extended mouse survival in a chemoresistant model and significantly improved chemotherapy response in a chemo-sensitive model. In summary, we propose a new therapeutic strategy for the treatment of metastatic OvCa. Show less

Post-COVID syndrome (PCS) is characterized by a polymorphism of symptoms with hypothetical pathophysiological mechanisms. Here, we aimed to analyze the profile of inflammatory cytokines in patients with PCS and to study the relationship between this profile, the clinical symptoms as well as the endothelial function in PCS. Our analytical study involved all eligible patients (n = 66) with PCS included from April 2021 to December 2021. The serum concentration of cytokines IFN-γ, IL-1α, IL-1β, IL-6, IL-8, IL-10, IL-12p70, IL-27, IP-10, MCP-1 and TNF-α was quantified by flow cytometry. Endothelial function was explored by assessing microvascular flow and reactivity using thermal probes. A comparative study was carried out according to the presence of each PCS symptom. The average age of our patients was 55.9 ± 16.2 years. The sex ratio was 0.69. Forty-one patients (62%) presented with a severe form of acute infection. The most frequently reported symptoms were dyspnea (67%), fatigue (50%), and memory problems (32%). Fifty-seven patients (86%) had endothelial dysfunction. The majority of patients had increased levels of IP-10 (100%), IL-8 (95%), IFN-γ (95%), MCP-1 (80%), and TNF-α (70%). The serum concentration of IL-10 was below the threshold of quantification in 89% of subjects. The severe form of acute infection was associated with elevated IL-10, MCP-1, and IL-27. Increased IL-6 and IL-27 levels were associated with fatigue while IL-8 concentrations were higher in patients who reported dyspnea. Elevation of IL-8 level was more common in patients with profound impairment of endothelial function. Our results further support the presence of endothelial dysfunction in PCS and show an elevation of pro-inflammatory cytokines with a downmodulation of the IL-10- anti-inflammatory response. In addition, immuno-clinical phenotypes emerge, such as an inflammatory profile mediated by IL-6 and IL-27 in fatigue and IL-8 in dyspnea. The identification of immuno-clinical phenotypes would allow a better understanding of the pathophysiology of PCS symptoms. Show less

Several studies provide evidence for a role of serum cytokines imbalance including IL-10 and IL-27 in immune thrombocytopenia pathogenesis and prognosis. The aim of this study was designed to investigate the role of serum levels of IL-10 and IL-27 in prognosis the efficiency of treatment in thrombocytopenic Iraqi children. This case controls study was carried out at Department of Biochemistry, College of Medicine, University of Baghdad, during the period from October 2023 to March 2024. It included 88 children, 63 children previously diagnosed with immune thrombocytopenia, and 25 apparently healthy children who served as control group. The included immune thrombocytopenic children were sub-grouped according to their treatment into three groups: Romiplostim group (group 1), Prednisolone group (group 2), Prednisolone and intravenous immunoglobulin (IVIG) or Prednisolone and mycophenolate group (group 3). Investigations included serum level measurements of IL-10 and IL-27 by using enzyme linked immunosorbent assay ELISA. Platelet count of each included children was measured by Huma Count 30 TS Human, Germany. The mean (±SEM) values of serum IL-10 and IL-27 levels of immune thrombocytopenic children were insignificantly lower than that of controls. In addition, there was non- significant differences in serum levels of IL-10 and IL-27 among and between the three groups of patient children. The mean value of platelet count of patient children was significantly increased by all types of treatment in whole immune thrombocytopenic children (117.48±18.15*10⁹/L). Measurement of serum IL-10 and IL-27 are helpful biomarker in prognosis of thrombocytopenia irrespective of type of treatment. Show less

Inflammatory cytokines have crucial roles in the pathogenesis of tuberculosis (TB), and interleukin (IL)-27 and IL-35 have a pro-inflammatory and anti-inflammatory effect on many diseases, including infectious diseases. Therefore, we evaluated the relationship between Show less

Interleukin (IL)-41, a type of cytokine also known as Metrnl, is involved in the pathogenesis of various inflammatory and immune-related diseases. However, its role in Ankylosing Spondylitis (AS), a field yet to be explored, remains a mystery. This study therefore assesses the diagnostic utility of IL-41 in patients with AS and examines the correlations among IL-41 levels, disease activity, and patients' demographic and clinical data. Such novel insights could have significant implications for the diagnosis and management of AS. Eighty-eight patients diagnosed with AS were enrolled from the Rheumatology Unit at Baghdad Teaching Hospital. Participants were categorized into two groups based on disease status: inactive (n = 44) and active (n = 44). Additionally, 44 matched healthy individuals were included as controls. Comprehensive medical histories were obtained, including disease duration, body mass index, sex, and age. Laboratory parameters related to the disease-such as C-reactive protein, human leukocyte antigen (HLA-B27), and rheumatoid factor-were also measured. Serum IL-41 levels were quantified using an enzyme-linked immunosorbent assay. The study revealed a significant difference in levels of IL-41 in patients with AS (17.721±0.705 ng/L) compared to controls (8.495±0.984 ng/L; P = 0.009). The mean serum IL-41 concentration was highest in the active group (23.037±5.268 ng/L), followed by the inactive group (12.411±1.672 ng/L; p = 0.001) and controls (8.495±0.984 ng/L). Serum IL-41 levels demonstrated strong validity for diagnosing AS, with a cutoff value of ≥ 9.35 ng/mL and an area under the curve of 0.991. The sensitivity, specificity, and accuracy were 97.7%, 79.5%, and 92.38%, respectively (p = 0.002). IL-41 is a potential new diagnostic biomarker for AS and associated with patient's disease activity. These insights could potentially transform the way we diagnose and manage AS, offering new avenues for improved patient care and outcomes. Show less

COVID-19 and other pandemic viruses continue being important for public health and the global economy. Therefore, it is essential to explore the pathogenesis of COVID-19 more deeply, particularly its association with inflammatory and antiviral processes. In this study, we used the RNA-seq technique to analyze mRNA and non-coding RNA profiles of human peripheral blood mononuclear cells (PBMCs) from healthy individuals after SARS-CoV-2 in vitro exposure, to identify pathways related to immune response and the regulatory post-transcriptional mechanisms triggered that can serve as possible complementary therapeutic targets. Our analyses show that SARS-CoV-2 induced a significant regulation in the expression of 790 genes in PBMCs, of which 733 correspond to mRNAs and 57 to non-coding RNAs (lncRNAs). The immune response, antiviral response, signaling, cell proliferation and metabolism are the main biological processes involved. Among these, the inflammatory response groups the majority of regulated genes with an increase in the expression of chemokines involved in the recruitment of monocytes, neutrophils and T-cells. Additionally, it was observed that exposure to SARS-CoV-2 induces the expression of genes related to the IL-27 pathway but not of IFN-I or IFN-III, indicating the induction of ISGs through this pathway rather than the IFN genes. Moreover, several lncRNA and RNA binding proteins that can act in the cis-regulation of genes of the IL-27 pathway were identified. Our results indicate that SARS-CoV-2 can regulate the expression of multiple genes in PBMCs, mainly related to the inflammatory and antiviral response. Among these, lncRNAs establish an important mechanism in regulating the immune response to the virus. They could contribute to developing severe forms of COVID-19, constituting a possible therapeutic target. Show less

To identify age-related plasma extracellular vehicle (EVs) phenotypes in healthy adults. EV proteomics by high-resolution mass spectrometry to evaluate EV protein stability and discover age-associated EV proteins (n=4 with 4 serial freeze-thaws each); validation by high-resolution flow cytometry and EV cytokine quantification by multiplex ELISA (n=28 healthy donors, aged 18-83 years); quantification of WI-38 fibroblast cell proliferation response to co-culture with PKH67-labeled young and old plasma EVs. The EV samples from these plasma specimens were previously characterized for bilayer structure, intra-vesicle mitochondria and cytokines, and hematopoietic cell-related surface markers. Compared with matched exo-EVs (EV-depleted supernatants), endo-EVs (EV-associated) had higher mean TNF-α and IL-27, lower mean IL-6, IL-11, IFN-γ, and IL-17A/F, and similar mean IL-1β, IL-21, and IL-22 concentrations. Some endo-EV and exo-EV cytokine concentrations were correlated, including TNF-α, IL-27, IL-6, IL-1β, and IFN-γ, but not IL-11, IL-17A/F, IL-21 or IL-22. Endo-EV IFN-γ and exo-EV IL-17A/F and IL-21 declined with age. By proteomics and confirmed by flow cytometry, we identified age-associated decline of fibrinogen (FGA, FGB and FGG) in EVs. Age-related EV proteins indicated predominant origins in the liver and innate immune system. WI-38 cells (>95%) internalized similar amounts of young and old plasma EVs, but cells that internalized PKH67-EVs, particularly young EVs, underwent significantly greater cell proliferation. Endo-EV and exo-EV cytokines function as different biomarkers. The observed healthy aging EV phenotype reflected a downregulation of EV fibrinogen subpopulations consistent with the absence of a pro-coagulant and pro-inflammatory condition common with age-related disease. Show less

Currently, there is a lack of serum biomarkers that can accurately predict the short-term prognosis of enterogenic sepsis. 99 patients with enterogenic sepsis were categorized based on their Acute Gastrointestinal Injury (AGI) grade on the third day of ICU admission into four groups: no AGI, AGI grade I, AGI grade II, and AGI (III+IV). Additionally, patients were classified into survival and death groups according to their 28-day clinical outcomes. Peripheral venous blood samples were collected to measure levels of interleukin (IL)-27, intestinal fatty acid-binding protein (IFABP), and diamine oxidase (DAO). Receiver operating characteristic (ROC) curves were generated to assess the ability of IL-27, IFABP, and DAO to predict the short-term prognosis of patients with enterogenic sepsis. On the third day, both the survival and death groups exhibited elevated serum levels of IL-27 and IFABP compared to the first day, while levels of DAO were lower than those observed on day one. Furthermore, a significant positive correlation was observed between IL-27 and both IFABP and DAO, with stronger correlations evident on day three compared to day one. As the Acute Gastrointestinal Injury (AGI) grading increased, levels of IL-27, IFABP, and DAO rose correspondingly, correlating with a gradual decrease in survival rates, all demonstrating statistical significance (all P < 0.05). The Area Under the Curve (AUC) values for IL-27, IFABP, and DAO on the third day, predicting short-term prognosis for intestinal sepsis patients, were 0.714, 0.772, and 0.724, respectively. Notably, these values surpassed those of the first day, with IFABP on the third day exhibiting the highest predictive capability. IL-27, IFABP, and DAO levels measured on the third day of hospitalization can accurately predict the short-term prognosis of enterogenic sepsis. Show less

In this study, we aimed to investigate the relationship between the intraocular levels of inflammatory factors and myopia-related retinal vascular and neuronal degeneration. One hundred and forty-seven patients with Implantable Collamer Lens (ICL) implantation were enrolled and all participants received comprehensive ophthalmic examination. About 100~150 ul of aqueous humor was collected immediately before ICL surgery. The levels of inflammatory factors including Aggrecan, April, BAFF, CCL5, CD163, Chi3l1, gp130, IL-6Rα, IL-8, IL-10, IL-11, IL-12, IL-19, IL-27, IL-28A, IL-34, IFN-β, IFN-γ, MMP-1, MMP-2, MMP-3 and PTX3 in the aqueous humor were measured using the Luminex Multiplexing system. Results showed that aqueous humor levels of pro-inflammatory factors Chi3l1, IL-6Rα, IL-8, IL-12, IL-27, inflammation-related cytokines April, BAFF and IL-34 progressively increased from the progression of myopic retinopathy. Conversely, the aqueous levels of IL-11 and Aggrecan gradually decreased from the progression of myopic retinopathy. Correlation analysis showed that the intraocular levels of Chi3l1, IL-6Rα, IL-8, IL-27 and BAFF were negatively correlated with retinal vascular density. The intraocular level of IL-6Rα was negatively correlated with retinal neuronal thickness. Protein-Protein Interaction (PPI) analysis revealed that Chi3l1 and Aggrecan were the upstream cytokines that affect IL-10 and IL-8 in the pathological myopic eyes. KEGG pathway analysis showed that cytokine-cytokine receptor interaction, JAK-STAT signaling pathway, rheumatoid arthritis, and chagas disease were influenced by these altered inflammatory factors (adjusted p-value<0.001). The production of inflammatory factors in the eyes of individuals with high myopia and pathological myopia was altered, and the elevated levels of intraocular pro-inflammatory factors such as Chi3l1, IL-6Rα, and IL-8 were closely associated with myopia-related retinal microvascular and neurodegeneration. Show less

The objective of this study was to investigate possible immune cytokine trends throughout a week-long surgical simulation mass-casualty training session in order to determine the effects of stress inoculation on the immune system. Thirty-seven military medical students participated in a hyper-realistic surgical simulation training event conducted at Strategic Operations site in San Diego, California. Salivary samples were collected every morning of the stress training exercise for 4 consecutive days. Cortisol, along with a panel of 42 immune cytokines, was measured using multiplex enzyme-linked immunosorbent assays from Eve Technologies. The determined concentrations were averaged and plotted on a scatter plot, and then points were fit to a second-order polynomial trendline of best fit to measure. The cytokines epidermal growth factor, growth-related oncogene-α, interleukin (IL)-1α, and platelet-derived growth factor-AA followed a noted pattern of cortisol decrease throughout the week. In addition, cytokines IL-27, granulocyte colony stimulating factor, IL-10, and IL-13 demonstrated a late peak, followed by a return to baseline at the conclusion of training. Finally, the cytokine monocyte chemoattractant protein-1 displayed a decline throughout the week followed by an increase on the last day of stress training. Altogether, these results help to identify important biomarkers that may help to improve long-term stress adaptation and prevent post-traumatic stress disorder following exposure to repeated stress. Show less

Innate lymphoid cells (ILCs) play an important role in maintaining tissue homeostasis and various inflammatory responses. ILCs are typically classified into three subsets, as is the case for T-cells. Recent studies have reported that IL-10-producing type 2 ILCs (ILC2 Show less

Nine soluble ligands [interleukin-6 (IL-6), interleukin-11 (IL-11), leukemia inhibitory factor (LIF), oncostatin M (OSM), ciliary neurotrophic factor (CNTF), cardiotrophin-1 (CT-1), cardiotrophin-like cytokine, interleukin-27 (IL-27), and interleukin-31] share the ubiquitously expressed transmembrane protein-glycoprotein-130 beta-subunit (gp130) and thus form IL-6 family cytokines. Proteins that may be important for cancerogenesis, CT-1, IL-11, IL-27, LIF, OSM, and CNTF, belong to the superfamily of IL-6. Cytokines such as IL-6, IL-11, and IL-27 are better investigated in comparison with other members of the same family of cytokines, eg, CT-1. Gp130 is one of the main receptors through which these cytokines exert their effects. The clinical implication of understanding the pathways of these cytokines in oncology is that targeted therapy to inhibit or potentiate cytokine activity may lead to remission in some cases. Show less

Interleukin-27 (IL-27) is known to play opposing roles in immunology. The present paper considers, specifically, the role IL-27 plays in cancer immunotherapy when combined with immune checkpoint inhibitor anti-PD-1. We first develop a mathematical model for this combination therapy, by a system of Partial Differential Equations, and show agreement with experimental results in mice injected with melanoma cells. We then proceed to simulate tumor volume with IL-27 injection at a variable dose F and anti-PD-1 at a variable dose g. We show that in some range of "small" values of g, as f increases tumor volume decreases as long as fShow less

Heart failure (HF) is associated with cytokine activation and inflammation. Experimental evidence suggests that plasma interleukin-17 (IL-17) is associated with myocardial fibrosis and cardiac dysfunction in HF. IL-17D, a subtype of IL-17 originates from particular tissues such as the heart. However, there is very limited data on the IL-17 cytokine family in patients with HF. Therefore, we investigated the association between circulating IL-17D levels, clinical characteristics and outcome in a large cohort of patients with heart failure. Plasma IL-17D was measured in 2032 patients with HF from 11 European countries using a proximity extension assay. The primary outcome was a composite of HF hospitalization or all-cause mortality. Patients with higher plasma IL-17D concentrations were more likely to have atrial fibrillation (AF), renal dysfunction and heart failure with preserved ejection fraction (HFpEF) and had higher plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) concentrations (all p < 0.001). IL-17D was not associated with interleukin-6 (IL-6) or C-reactive protein (CRP) concentrations. After adjustment for confounders in a multivariable Cox regression analysis, patients in the highest quartile of plasma IL-17D had a significantly increased risk of the composite outcome of HF hospitalization or all-cause mortality compared to patients in the lowest quartile [Hazard ratio (HR) 1.28, 95% confidence interval (CI) 1.05-1.57]. In patients with HF, elevated plasma IL-17D concentrations are associated with higher plasma NT-proBNP concentrations and a higher prevalence of AF and renal dysfunction. High IL-17D concentrations are independently associated with worse outcome. Show less