Serum IL-18 Levels Research Articles

Serum IL-27 levels increase in subjects with hypothyroidism and are negatively correlated with the occurrence of nonalcoholic fatty liver disease.

The level of serum interleukin-27 (IL-27) was significantly decreased in the obesity group. After injection of IL-27, obese mice showed significant weight loss,reduced fat accumulation, improved insulin resistance and hepatic steatosis.IL-27 plays a key role in the regulation of metabolic processes, but there are scarce data on circulating IL-27 levels in hypothyroidism. The purpose of this study was to assess the serum levels of IL-27 in patients with hypothyroidism and its relationship with NAFLD. 185 participants were included in this cross-sectional survey. According to thyroid function, the subjects were classified into three groups: euthyroidism (n = 55), subclinical hypothyroidism (n = 53), and hypothyroidism (n = 77). Serum IL-27 concentrations were measured by ELISA. Serum IL27 levels were significantly higher in subclinical hypothyroidism and hypothyroidism groups than in the euthyroidism group. Serum IL27 levels had a negative correlation with HOMA-IR,FBG,TG, subcutaneous fat,and visceral fat, and had a positive correlation with HDL-C (P< 0.05). Furthermore, logistic regression analysis indicated that IL-27 levels, HOMA-IR, and visceral fat showed significant associations with NAFLD after complete adjustment (P< 0.05). ROC curves showed that theoptimal cut-off value of serum IL-27 for discriminating NAFLD was 95.87pg/mL. The area under the ROC curve was 77.3% (95% CI = 0.694-0.851, p < 0.001). Serum IL-27 levels demonstrated a compensatory increase in patients with subclinical hypothyroidism or hypothyroidism and showed an independent association with NAFLD. Circulating IL-27 levels could predict the occurrence of NAFLD in hypothyroidism. These results suggested that altering the circulating levels of IL-27 may be a potential therapeutic target for NAFLD.

BAFFR expression in circulating T follicular helper (CD4+CXCR5+PD-1+) and T peripheral helper (CD4+CXCR5-PD-1+) cells in systemic lupus erythematosus.

Circulating T follicular helper (cTfh) and T peripheral helper (Tph) subpopulations are shown to be higher in systemic lupus erythematosus (SLE) patients and have been involved in promoting extrafollicular B cell responses. However, a possible association with the B cell activating factor (BAFF), a cytokine mainly related to B cell responses and disease activity in SLE, has not been investigated. Therefore, this study aimed to evaluate the association of cTfh and Tph subpopulations with the BAFF system expression and clinical activity in SLE patients. This study included 43 SLE patients and 12 healthy subjects (HS). The identification of cTfh (CD4+CXCR5+PD-1+), Tph (CD4+CXCR5-PD-1+) cells, expression of membrane-bound BAFF (mBAFF), BAFFR, TACI, BCMA, and intracellular IL-21 was performed by flow cytometry. Serum levels of IL-21, CXCL13, and BAFF were analyzed using ELISA. The SLEDAI-2K score was used to evaluate disease activity in SLE patients. Compared with HS, SLE patients showed a significantly increased percentage of cTfh and Tph cells, higher in patients with clearly active disease. SLE patients had markedly higher IL-21-producing cTfh and Tph cells than HS. Both subpopulations were positively correlated with the disease activity in SLE patients. Tph cells were negatively correlated with CD19+CXCR5+ B cells and positively correlated with CD19+CXCR5- B cells. A low expression of mBAFF and their receptors TACI and BCMA was found on cTfh and Tph cells in SLE patients and HS. However, SLE patients with clearly active disease showed decreased expression of BAFFR on cTfh and Tph subpopulations than patients with mildly active/nonactive disease. Serum IL-21, CXCL13, and BAFF levels were higher in SLE patients than in HS. Levels of CXCL13 were correlated with disease activity. Non-significant correlations were observed among T cell subpopulations and IL-21, CXCL13, and BAFF levels. This study emphasizes the importance of cTfh and Tph cells in SLE pathogenesis. Besides the importance of IL-21, our results suggest that BAFFR could play a role in cTfh and Tph subpopulations in the autoimmunity context.

Analysis of IL-10 and IL-35 in dipeptidyl peptidase-4 inhibitor-related bullous pemphigoid.

The association between immunoregulatory cytokines, such as interleukin (IL)-10 or IL-35, and dipeptidyl peptidase-4 inhibitor (DPP4i)-related bullous pemphigoid (BP) has not been evaluated. Serum IL-10 and IL-35 levels were measured in 39 patients with BP (24 males and 15 females; 6 DPP4i-related and 33 DPP4i-unrelated BP patients) and 10 healthy controls. The number of CD26+ cells in the dermis around bulla on sections was counted immunohistochemically for 12 patients (six patients with DPP4i-related BP and six randomly sampled patients with DPP4i-unrelated BP). Patients with DPP4i-related BP had lower levels of serum eosinophils (DPP4i-related vs. DPP4i-unrelated BP: 476.1 ± 234.0 vs. 911.3 ± 948.8/μL; p = 0.537) and a higher rate of infiltrating CD26+ cells (32.9 ± 7.1% vs. 15.7 ± 4.4%; p = 0.01). There were no significant differences in serum IL-10 (6.77 ± 0.24 vs. 6.84 ± 0.20 pg/mL), serum IL-35 (2.63 ± 0.17 vs. 2.63 ± 0.21 pg/mL), serum anti-BP180NC16a antibodies (67.31 ± 37.4 vs. 76.18 ± 54.59 U/mL) and Bullous Pemphigoid Disease Area Index before treatment in this study. Serum IL-10 and IL-35 levels do not increase in patients with BP and may not be a candidate for a therapeutic target for BP. An increase in CD26+ cells might be associated with DPP4i-related BP.

Defective Treg generation and increased type 3 immune response in leukocyte adhesion deficiency 1

In 15 Turkish LAD-1 patients and controls, we assessed the impact of pathogenic ITGB2 mutations on Th17/Treg differentiation and functions, and innate lymphoid cell (ILC) subsets.The percentage of peripheral blood Treg cells, in vitro-generated induced Tregs differentiated from naive CD4+ T cells were decreased despite the elevated absolute counts of CD4+ cells in LAD-1 patients. Serum IL-23 levels were elevated in LAD-1 patients. Post-curdlan stimulation, LAD-1 patient-derived PBMCs produced more IL-17A. Additionally, the percentages of CD18-deficient Th17 cells expanded from total or naïve CD4+ T cells were higher. The blood ILC3 subset was significantly elevated in LAD-1. Finally, LAD-1 PBMCs showed defects in trans-well migration and proliferation and were more resistant to apoptosis.Defects in de novo generation of Tregs from CD18-deficient naïve T cells and elevated Th17s, and ILC3s in LAD-1 patients' peripheral blood suggest a type 3-skewed immunity and may contribute to LAD-1-associated autoimmune symptoms.

Efficacy and immunological changes of sublingual immunotherapy in pediatric allergic rhinitis

BackgroundAllergen-specific immunotherapy, including subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT), improves the disease progression of allergic rhinitis (AR). SCIT and SLIT exhibit similar efficacy, but SLIT has less systemic reactions. However, few studies have investigated the underlying mechanisms of SLIT treatment. In this study, we explored the efficacy of SLIT under different treatment durations and immunological changes. MethodsThis retrospective study was conducted from August 2017 to August 2022 in our hospital. A total of 314 children who underwent SLIT were divided into the following groups based on their treatment duration: the 1 year group (6 months–1 year), the 2 years group (1–2 years), and the 3 years group (2–3 years). The treatment efficacy was confirmed using a combined symptom and medication score (SMS). Multiple serum cytokines were measured using Luminex. Various immune cells in PBMCs were determined using flow cytometry. ResultsThe total nasal symptom score (TNSS), rescue medication score (RMS), and SMS of the 3 years group was significantly different from those of the 1 years and 2 years groups. At the end of the 2 years following cessation of SLIT, the following results were observed in the 3 years group: 1) the TNSS, RMS, and SMS had significantly improved, 2) the serum IL-10, TGF-beta, and IL-35 levels had increased significantly, and 3) the percentages of regulatory T cell, regulatory B cell, and follicular regulatory T cell increased significantly. ConclusionOur results suggest that 3 years of SLIT is necessary for long-term effects and continued immunological changes.

Clinical significance of serum cytokine profiles for differentiating between Kawasaki disease and its mimickers

ObjectivesTo investigate the clinical significance of serum cytokine profiles for differentiating between Kawasaki disease (KD) and its mimickers. MethodsPatients with KD, including complete KD, KD shock syndrome (KDSS), and KD with macrophage activation syndrome (KD-MAS), and its mimickers, including multisystem inflammatory syndrome in children, toxic shock syndrome, and Yersinia pseudotuberculosis infection, were enrolled. Serum levels of interleukin (IL)-6, soluble tumor necrosis factor receptor type II (sTNF-RII), IL-10, IL-18, and chemokine (C-X-C motif) ligand 9 (CXCL9) were measured using enzyme-linked immunosorbent assay and compared them with clinical manifestations. ResultsSerum IL-6, sTNF-RII, and IL-10 levels were significantly elevated in patients with KDSS. Serum IL-18 levels were substantially elevated in patients with KD-MAS. Patients with KD-MAS and KD mimickers had significantly elevated serum CXCL9 levels compared with those with complete KD. Area under the receiver operating characteristic curve analysis showed that serum IL-6 was the most useful for differentiating KDSS from the others, IL-18 and CXCL9 for KD-MAS from complete KD, and CXCL9 for KD mimickers from complete KD and KD-MAS. ConclusionSerum cytokine profiles may be useful for differentiating between KD and its mimickers.

Dupilumab aggravates Sézary syndrome: The importance of accurate pathological diagnosis

We report a case of Sézary syndrome aggravated by dupilumab. Although a diagnosis of atopic dermatitis was made previously, our retrospective diagnosis was cutaneous T-cell lymphoma. A 72-year-old woman was referred for evaluation of erythema over her entire body. She had received a diagnosis of atopic dermatitis (AD) based on skin biopsy elsewhere 7 years earlier. Since her symptoms were resistant to topical corticosteroids and oral antihistamines, dupilumab was started. She noticed peripheral lymph node enlargement 11 months after the commencement of dupilumab. Physical examination revealed generalized erythroderma with desquamation (Figure 1A,B) and lymphadenopathy in the neck, axilla, and inguinal region. A biopsy from her abdomen showed dense infiltrations of atypical lymphoid cells in the upper dermis with epidermotropism (Figure 1C,D). Immunohistochemically, the infiltrating cells were positive for CD3 and CD4; CD8 was almost negative. There was a 50% deletion of CD7 (Figure 1E–H). Her peripheral blood (PB) white blood cell count was 7660/μL, with 35% abnormal lymphocytes (2681/μL). Although CD4+/CD26− or CD4+/CD7− cells were not assessed, CD4/CD8 ratio was 10.59.1, 2 Human T-lymphotropic virus-1 antibody was negative. Monoclonal gene rearrangement of T-cell receptor β-chain was identified in her PB by Southern blot analysis. Inguinal lymph node biopsy showed partial effacement by atypical lymphocytes. The diagnosis was Sézary syndrome (SS), stage IVA2 (T4N3MXB2). Taking into account the risk of tumor lysis syndrome due to high tumor burden, we selected conventional multiagent chemotherapy as an initial therapy before using a molecular-targeted drug. Dupilumab was discontinued; cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) were started. After two cycles of CHOP, biweekly intravenous mogamulizumab was introduced. Her skin lesions gradually improved. The PB abnormal lymphocyte count decreased. Her disease was well controlled with mogamulizumab for 17 months. We reviewed the previous biopsy specimen. Dense dermal infiltrates with atypical cells and epidermotropism were seen (Figure 1I,J). These infiltrates were positive for CD3 and CD4. CD8-positive cells were sparse. There was a 30% deletion of CD7 (Figure 1K–N). The atypical cells were CCR4+ and CD68−. Although a diagnosis of AD was made previously, our retrospective diagnosis was cutaneous T-cell lymphoma (CTCL). Dupilumab is a monoclonal antibody which inhibits both IL-4 and IL-13 signaling pathways by binding specifically to the α subunit of the IL-4 receptor. Several cases of CTCL that developed or worsened after dupilumab use have been reported. A proposed mechanism of CTCL due to dupilumab is the involvement of IL-13 receptor α2 (IL-13Rα2), which is expressed on CTCL cells and promotes tumor progression. When dupilumab blocks IL-4 and IL-13 receptors, serum IL-13 levels increase. Because dupilumab inhibits IL-13Rα1 but not IL-13Rα2 signaling, increased IL-13 levels due to dupilumab stimulate IL-13Rα2, leading to the activation and proliferation of lymphoma cells.3 To our knowledge, there are 36 cases3-19 of CTCL worsened by dupilumab based on the diagnosis of AD or eczema have been reported. Of these 36 patients, 18 underwent skin biopsy prior to dupilumab therapy; no evidence of CTCL was described in 16 patients.3-10 In one remaining patient, the authors re-evaluated the biopsy specimen taken before dupilumab treatment and revised the diagnosis to early CTCL-not otherwise specified.10 In another patient, the first skin biopsy taken before dupilumab was compatible with AD; however, the diagnosis of mycosis fungoides was made by the second biopsy taken on the first day of dupilumab treatment. After 6 months of dupilumab treatment, the third biopsy turned out CD30-positive anaplastic large-cell lymphoma.11 When using dupilumab for AD, clinicians should be alert to the development or worsening of CTCL. Skin biopsy with immunohistochemical examination is strongly recommended before dupilumab therapy, especially in patients with erythroderma and elderly patients. The authors declare no conflict of interest. Approval of the research protocol: N/A. Informed Consent: N/A. Registry and the Registration No.: N/A. Animal Studies: N/A.

Correlation between elevated serum interleukin-1β, interleukin-16 levels and psychiatric symptoms in patients with schizophrenia at different stages

BackgroundThere is increasing evidence that immune dysfunction plays an important role in the pathogenesis of schizophrenia. Meso Scale Discovery (MSD) is bioanalytical method, which can detect serum inflammatory factors in patients. MSD has higher sensitivities, capturing a narrower range of proteins compared to other methods typically used in similar studies. The present study was aimed to explore the correlation between the levels of serum inflammatory factors and psychiatric symptoms in patients with schizophrenia at different stages and investigate a wide panel of inflammatory factors as independent factors for the pathogenesis of schizophrenia.MethodsWe recruited 116 participants, including patients with first-episode schizophrenia (FEG, n = 40), recurrence patients (REG, n = 40) with relapse-episode schizophrenia, and a control group (healthy people, HP, n = 36). Patients are diagnosed according to the DSM -V. The plasma levels of IFN-γ, IL-10, IL-1β, IL-2, IL-6, TNF-α, CRP, VEGF, IL-15, and IL-16 were tested by the MSD technique. Patient-related data was collected, including sociodemographic data, positive and negative symptom scale (PANSS), and brief psychiatric rating scale (BPRS) and subscale scores. The independent sample T test, χ2 test, Analysis of covariance (ANCOVA), the least significant difference method (LSD), Spearman’s correlation test, binary logistic regression analysis and ROC curve analysis were used in this study.ResultsThere were significant differences in serum IL-1β (F = 2.37, P = 0.014) and IL-16 (F = 4.40, P < 0.001) levels among the three groups. The level of serum IL-1β in the first-episode group was significantly higher than in the recurrence group (F = 0.87, P = 0.021) and control group (F = 2.03, P = 0.013), but there was no significant difference between the recurrence group and control group (F = 1.65, P = 0.806). The serum IL-16 levels in the first-episode group (F = 1.18, P < 0.001) and the recurrence group (F = 0.83, P < 0.001) were significantly higher than in the control group, and there was no significant difference between the first-episode group and the recurrence group (F = 1.65, P = 0.61). Serum IL-1β was negatively correlated with the general psychopathological score (GPS) of PANSS (R=-0.353, P = 0.026). In the recurrence group, serum IL-16 was positively correlated with the negative score (NEG) of the PANSS scale (R = 0.335, P = 0.035) and negatively correlated with the composite score (COM) (R=-0.329, P = 0.038). In the study, IL-16 levels were an independent variable of the onset of schizophrenia both in the first-episode (OR = 1.034, P = 0.002) and recurrence groups (OR = 1.049, P = 0.003). ROC curve analysis showed that the areas under IL-16(FEG) and IL-16(REG) curves were 0.883 (95%CI:0.794–0.942) and 0.887 (95%CI:0.801–0.950).ConclusionsSerum IL-1β and IL-16 levels were different between patients with schizophrenia and healthy people. Serum IL-1β levels in first-episode schizophrenia and serum IL-16 levels in relapsing schizophrenia were correlated with the parts of psychiatric symptoms. The IL-16 level may be an independent factor associating with the onset of schizophrenia.

Immunological signature of patients with thymic epithelial tumors and Good syndrome: Correlation with clinical outcome.

e20648 Background: Thymic epithelial tumors (TETs) are extremely rare and heterogenous neoplasms, associated with immune dysregulation. Recognized prognostic factors are TNM stage and the Masaoka-Koga classification. To the best of our knowledge, no study has been conducted to investigate the correlation between immunophenotype, level of cytokines, chemochines and clinical outcome in TETs patients. The aim of this study was to evaluate the correlation of immunological signature and long-term outcome in patients with TETs and Good Syndrome (GS). Methods: From May 2019 to October 2022, consecutive patients with TETs and GS, referred to the Rare Tumors Coordinating Center of Campania Region (CRCTR) of Federico II of Naples, were enrolled. The immunophenotype of monocytes, neutrophils, eosinophils, CD4+ T cells, CD8 + T cells, B-cells, NK cells and NKT-cells, T regulatory cells, and the evaluation of serum levels of cytokines, chemokines and growth factors were assessed using the 8-color immunophenotyping kit, Treg detection kit and pre-formed Kits by Bioplex multiplex, respectively. D’Agostino-Pearson normality test was used to evaluate whether the continuous data were normally distributed, and a two-tailed t-test for independent samples was used. Overall survival (OS) analysis was performed generating Kaplan-Meier curves and Cox Univariate models for the considered categorical stratifications. p-values &lt; 0.05 were considered statistically significant. Results: A total of 24 consecutive TETs patients were included in the study: 13 (54.17%) patients were male and 11 (48.83%) were female, with a median age of 54.96 ± 9.6 years. Tumor histology included 20 thymoma, and 4 thymic carcinoma. Autoimmune diseases were found in 13 patients all of whom had thymoma. At the time of this analysis, 5 (20.83%) patients had no evidence of disease (NED) by imaging and were in follow-up, 17 (70.83%) patients were still alive. The analysis of leucocytes did not show statistically significant association with clinical outcome of TETs patients. On the contrary, a statistically significant correlation between serum concentration of IL-6 and OS was found with lower levels of IL-6 associated with poorer prognosis (HR: 9.654; p = 0.016). In addition, we found a statistically significant reduction of IL-2 (p = 0.04), IL-15 (p = 0.048), IL-5 (p = 0.03) and VEGF (p = 0.01) serum levels in patients with evidence of disease, as compared to NED patients. Conclusions: Overall, these findings suggest that measurement of IL-6 levels may be a useful parameter for identifying TETs patients with GS who have more aggressive diseases. Our preliminary data may be useful in the clinical management of this complex disease. Further studies are needed to better understand the pathophysiology and clinical implications of immunophenotype alterations in TETs patients.

Pharmacological Inhibition of Gasdermin D Suppresses Angiotensin II-Induced Experimental Abdominal Aortic Aneurysms.

Gasdermin D, a molecule downstream of the nucleotide-binding oligomerization domain-like receptor family pyrin domain containing inflammasome, forms the membrane pore for the secretion of interleukin (IL)-1β and IL-18, and also mediates pyroptosis. This study was to explore the influence of treatment with disulfiram, a small molecule inhibitor to gasdermin D, on the formation and progression of experimental abdominal aortic aneurysms (AAA). AAAs were induced in 10-week-old male apolipoprotein E deficient mice by subcutaneous infusion of angiotensin II (1000 ng/min/kg body weight) for 28 days via osmotic minipumps. Three days prior to angiotensin II infusion, disulfiram (50 mg/kg) or an equal volume of saline as the vehicle control was administered daily via oral gavage. The influence on experimental AAAs was analyzed by serial measurements of aortic diameters via ultrasonography, grading AAA severity and histopathology at sacrifice. Serum IL-1β and IL-18 levels, systolic blood pressure, total cholesterol, and triglyceride were also measured. Additional experiments assayed the influences on the cell viability and IL-1β secretion of in vitro activated macrophages. Disulfiram significantly reduced the enlargement, incidence, and severity of angiotensin II-induced experimental AAAs with attenuation of medial elastin breaks, mural macrophage accumulation, and systolic blood pressure. The AAA suppression was also associated with reduced systemic levels of IL-1β but not IL-18. However, disulfiram treatment had no impact on body weight gain and lipid levels in aneurysmal mice. Additionally, disulfiram treatment also markedly reduced the secretion of IL-1β from activated macrophages with a limited effect on cell viability in vitro. Gasdermin D inhibition by disulfiram attenuated angiotensin II-induced experimental AAAs with reduced systemic IL-1β levels and in vitro activated macrophage IL-1β secretion. Our study suggests that pharmacological gasdermin D inhibition may have translational potential for limiting clinical AAA progression.

Qiqilian ameliorates vascular endothelial dysfunction by inhibiting NLRP3-ASC inflammasome activation in vivo and in vitro

Context Previous studies have highlighted significant therapeutic effects of Qiqilian (QQL) capsule on hypertension in spontaneously hypertensive rats (SHRs); however, its underlying molecular mechanism remains unclear. Obejective We investigated the potential mechanism by which QQL improves hypertension-induced vascular endothelial dysfunction (VED). Materials and methods In vivo, SHRs were divided into four groups (20 per group) and were administered gradient doses of QQL (0, 0.3, 0.6, and 1.2 g/kg) for 8 weeks, while Wistar Kyoto rats were used as normal control. The vascular injury extent, IL-1β and IL-18 levels, NLRP3, ASC and caspase-1 contents were examined. In vitro, the effects of QQL-medicated serum on angiotensin II (AngII)-induced inflammatory and autophagy in human umbilical vein endothelial cells (HUVECs) were assessed. Result Compared with the SHR group, QQL significantly decreased thickness (125.50 to 105.45 μm) and collagen density (8.61 to 3.20%) of arterial vessels, and reduced serum IL-1β (96.25 to 46.13 pg/mL) and IL-18 (345.01 to 162.63 pg/mL) levels. The NLRP3 and ACS expression in arterial vessels were downregulated (0.21- and 0.16-fold, respectively) in the QQL-HD group compared with the SHR group. In vitro, QQL treatment restored NLRP3 and ASC expression, which was downregulated approximately 2-fold compared with that of AngII-induced HUVECs. Furthermore, QQL decreased LC3II and increased p62 contents (p < 0.05), indicating a reduction in autophagosome accumulation. These effects were inhibited by the autophagy agonist rapamycin and enhanced by the autophagy inhibitor chloroquine. Conclusion QQL effectively attenuated endothelial injury and inflammation by inhibiting AngII-induced excessive autophagy, which serves as a potential therapeutic strategy for hypertension.

Evaluation of serum adipocytokine and interleukin-18 levels in patients with epilepsy

Objective: Epilepsy is a neurological disease characterized by recurrent seizures. The underlying pathophysiological mechanisms in epilepsy are not fully known. Our aim is to investigate the relationship between serum adipocytokine and interleukin (IL)-18 levels in epilepsy patients receiving and not receiving antiepileptic therapy.&#x0D; &#x0D; Method: Our study was established as three groups. I: Epilepsy patients receiving antiepileptic therapy (n=30), II: Newly diagnosed epilepsy patients (n=30) and III: Control group (n=30). Serum adipocytokine and IL-18 levels were measured by enzyme-linked immunoassorbent assay method.&#x0D; &#x0D; Results: It was determined that serum adipocytokine and IL-18 levels were increased in epilepsy patients who received topiramate treatment and did not receive antiepileptic therapy compared to the control group. Serum glucose, total protein, cholesterol and albumin concentrations of patients who received antiepileptic treatment were decreased compared to the control group (p0.05). It was found that the body mass index (BMI) ratio of epilepsy patients who received antiepileptic treatment decreased and was significant compared to the control group and the group that did not receive treatment (p

Circulating Interleukin-23 Levels in Rheumatoid Arthritis and its Relationship to Disease Activity: a Systematic Review with Meta-Analysis

Background: Rheumatoid arthritis (RA) is a chronic and systemic autoimmune disease that is characterized by severe synovial inflammation, cartilage erosion, bone loss, and generalized vasculopathy. Although the immunologic mechanism of RA is still unclear, it is now thought to be a primarily Th17-driven disease. Along with other factors, IL-23 stimulates the expansion of Th17 cells from naive CD4+ T cells. Objective: The objective of this study is to assess the circulating levels of interleukin (IL)-23 in rheumatoid arthritis (RA) and determine the correlation between plasma/serum IL-23 levels and disease activity. So, we performed a systematic review with meta-analysis comparing plasma/serum IL-23 levels between patients with RA and controls and examined correlation coefficients between circulating IL-23 levels and disease activity Subjects and Methods: Using the following keywords: lenterleukin-23, IL-23, and rheumatoid arthritis, a comprehensive literature search was carried out in the following databases: PubMed, Scopus, Google Scholar, and Web of Science. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses standards were followed, and the review was registered in the PROSPERO International prospective register of systematic reviews with registration number CRD42022345901. Results were reported as standardized mean differences (SMDs) with a 95% confidence interval. All statistical analysis was performed using StatsDirect statistical software version 3.0.0 (StatsDirect Ltd., Cheshire, UK). A sensitivity analysis was conducted using the leave-one-out approach to test the robustness of the results. Results: The total sample size for the RA group included in our review was 408 cases, while the control group sample size was 244 cases. The serum IL-23 level in the RA group was significantly higher than the control group (pooled SMD = 3.5, 95% CI; 2.1: 4.8, P &lt; 0.0001) as compared to the control group. There were 8 studies with a total sample size of 402 that reported the correlation between IL-23 and DAS28-based RA activity. According to our findings, a significantly positive correlation between IL-23 and DAS28-based RA activity was found, with a weighted mean correlation of 0.57 (95% CI; 0.4: 0.75, P &lt; 0.0001). Conclusion: Our meta-analysis has shown that IL-23 circulatory levels are higher in RA patients and that there is a significant positive correlation between IL-23 and disease activity. Our findings emphasize the role that IL-23 may have in RA. More studies may be required to fully comprehend the involvement of IL-23 in RA.

Protective effect of the total flavonoids from Clinopodium chinense against LPS-induced mice endometritis by inhibiting NLRP3 inflammasome-mediated pyroptosis

Ethnopharmacological relevanceClinopodium chinense (Benth.) O. Kuntze (C. chinense) is a Chinese herbal medicine used in treating gynecological hemorrhagic diseases for hundreds of years. Flavonoids are one kind of the major components in C. chinense. The flavonoids of C. chinense (TFC) have a vital role in treating endometritis but the underlying therapeutic mechanisms of TFC against endometritis have been rarely reported. Aim of the studyTo elucidate the therapeutic effect and possible mechanisms of TFC against lipopolysaccharide (LPS)-induced endometritis in vivo and LPS-induced primary mouse endometrial epithelial cells (MEECs) injury in vitro. Materials and methodsThe holistic phytochemicals of the TFC and TFC-contained serum were screened and identified using UPLC-Q-TOF-MS. The model of endometritis was established by intrauterine injection of LPS (5 mg/mL) into female BALB/c mice, and the model mice were treated with TFC for 7 days. The value of MPO was measured by Myeloperoxidase assay kit, the pathological changes in the endometrium were evaluated using H&E staining and transmission electron microscope (TEM), the secretions of IL-18, IL-1β and TNF-α were determined by ELISA kits, the mRNA expressions of IL-18, IL-1β and TNF-α were determined by RT-PCR assay, and the protein levels of TLR4, IKBα, p-IKBα, p65, p-p65, caspase-1, ASC, NLRP3 and GSDMD were measured by Western blot. Subsequently, MEECs were isolated from the uterus of pregnant female mice, injured by LPS for 24 h and incubated with the TFC-contained serum. Finally, cell viability, LDH release, hoechst 33342/PI staining, immunofluorescence staining, scanning electron microscope observation, ELISA assay, RT-PCR detection and Western blot analysis were carried out to further validate the therapeutic effect and the underlying mechanisms of TFC. ResultsA total of 6 compounds in the plasma of mice after being intragastric administrated of TFC were identified. The results in vivo showed that TFC significantly reduced MPO value and alleviated pathological injury of the endometrium. Furthermore, TFC significantly decreased the serum IL-18, IL-1β and TNF-α levels, and the mRNA levels of IL-18, IL-1β and TNF-α. TFC also inhibited the expressions of TLR4, p-IKBα, p-p65, caspase-1, ASC, NLRP3 and GSDMD. Besides, compared with the model group in MEECs cells, TFC-contained serum prevented pyroptosis, decreased the levels of IL-18 and IL-1β, and inhibited the mRNA expressions of IL-18, IL-1β and GSDMD. TFC-contained serum also reversed the activation of NLRP3 inflammasome caused by nigericin, and restrainted the translocation of NF-κB into nuclear. ConclusionsTFC protects mice endometritis from the injury of LPS via suppressing the activation of NLRP3 inflammasome and pyroptosis, the underlying mechanisms of which were related to restraining the TLR4/NF-κB/NLRP3 pathway activation.

Euphorbium total triterpenes improve Freund's complete adjuvant-induced arthritis through PI3K/AKT/Bax and NF-κB/NLRP3 signaling pathways.

Euphorbium is the resinous secretion of Euphorbia resinifera Berg. According to the record, Euphorbium was first used by Roman doctors to treat the emperor's joint pain. In China, it is applied in folk medicine to treat damp-cold or mucous diseases, such as arthralgia and ascites, etc. This herb is used for rheumatoid arthritis and skin tumors in the folklore of northeastern Brazil. Triterpenes are mainly characteristic constituents of Euphorbium, and possibly possess anti-rheumatoid arthritis. To explore the preventive effect of Euphorbium total triterpenes (TTE) on Freund's complete adjuvant (FCA) induced arthritis in rats and its mechanism. TTE was extracted and isolated from Euphorbium, and its components were analyzed by HPLC. The safety of TTE was evaluated by an acute toxicity test in mice. Arthritis was induced in rats by injecting 0.2mL FCA into the right hind paw toe, except for the control group, which was given the same volume of physiological saline. Tripterygium Glycosides (TG, 7.5mg/kg) and TTE (32, 64 and 128mg/kg) were administered by gavage for 30 days. Body weights, paw swelling, and arthritic scores were measured during the experiment process. After 30 days, blood and joints were harvested to determine various indicators of arthritis. The contents of euphol and euphorbol in TTE were 47.03% and 18.77% respectively, and the maximal feasible dose of TTE in mice is 12 g/kg. The experimental results showed that arthritis indicators in rats deteriorated after FCA inducement compared with the control group. After treatment with TTE, the swelling degree and histopathological change of the hind paws in rats were significantly improved as well as arthritic score; the serum TNF-α, CRP, IL-1β, IL-6, IL-18 and RF levels in rats were significantly reduced; The expression of PI3K, AKT, P-AKT, Bcl-2, NF-κB, NLRP3 and Pro-caspase-1 protein in joint tissue were down-regulated, and the expression of Bax protein was up-regulated. The results suggested that TTE possessed anti-arthritis effects, and its mechanism may be related to its anti-inflammatory and immunomodulatory properties, as well as regulation of PI3K/AKT/Bax and NF-κB/NLRP3 signaling pathway.

Effect of entecavir plus peginterferon α-2a on hepatitis B virus-RNA, IL-21 expression level, immune function and prognosis in patients with hepatitis B

Combination of interferon and nucleotide analogues might be more effective in inhibiting replication of hepatitis B virus (HBV), thereby alleviating hepatic fibrosis and hepatocyte necrosis. Herein, we explored the impact of co-treatment of entecavir (ETV) and PEG-IFNα-2a on HBV-RNA, IL-21 level, immune function and prognosis in HBeAg-positive patients with low HBsAg level. Patients treated with ETV over 12 months received PEG-IFNα-2a treatment. Serum HBV markers and HBV-DNA were examined at 12, 24 and 48 weeks, and disappearance of HBsAg were measured at 24 weeks as an evaluation index for efficacy. Besides, levels of IL-21, serum albumin, and complement C3 were measured. During follow-up, we found that, HBsAg serological conversion appeared in 6.0% of all patients, with HBsAg disappearance in 18.1% and HBsAg &lt;10 IU/mL in 10.8%. The HBeAg level in non-disappearing group was lower than HBsAg disappearing group (P &lt;0.05) with AUC score of 0.720 for HBsAg suggested by HBeAg conversion rate (P &lt;0.05). Of note, HBsAg levels decreased at 12 weeks of treatment (≥0.5 log IU/mL) and HBsAg was prone to disappearance (P &lt;0.05). AUC of HBsAg disappearance predicted by the HBsAg levels at 12 weeks and 24 weeks were 0.810 (95% CI: 0.686–0.935, P = 0.000) and 0.842 (95% CI: 0.736–0.947, P = 0.000) compared with baseline. Combination of ETV and PEG-IFNα-2a resulted in enhancement of serum IL-21 level (210.803±72.477) and reduction of IL-21 expression (157.084±38.697). The IL-21 level was negatively correlated with immune function indicators serum albumin and serum complement C3. HBsAg conversion rate and early HBsAg changes are crucial to prediction of HBsAg disappearance. With ETV achieving great virological response, combination of ETV with PEG-IFNα-2a enhanced HBsAg loss, reducing IL-21 expression, and improving immune function in patients.

Atranorin inhibits NLRP3 inflammasome activation by targeting ASC and protects NLRP3 inflammasome-driven diseases.

Aberrant NLRP3 activation has been implicated in the pathogenesis of numerous inflammation-associated diseases. However, no small molecular inhibitor that directly targets NLRP3 inflammasome has been approved so far. In this study, we show that Atranorin (C19H18O8), the secondary metabolites of lichen family, effectively prevents NLRP3 inflammasome activation in macrophages and dendritic cells. Mechanistically, Atranorin inhibits NLRP3 activation induced cytokine secretion and cell pyroptosis through binding to ASC protein directly and therefore restraining ASC oligomerization. The pharmacological effect of Atranorin is evaluated in NLRP3 inflammasome-driven disease models. Atranorin lowers serum IL-1β and IL-18 levels in LPS induced mice acute inflammation model. Also, Atranorin protects againstMSU crystal induced mice gouty arthritis model and lowers ankle IL-1β level. Moreover, Atranorin ameliorates intestinal inflammation and epithelial barrier dysfunction in DSS induced mice ulcerative colitis and inhibits NLRP3 inflammasome activation in colon. Altogether, our study identifies Atranorin as a novel NLRP3 inhibitor that targets ASC protein and highlights the potential therapeutic effects of Atranorin in NLRP3 inflammasome-driven diseases including acute inflammation, gouty arthritis and ulcerative colitis.

Factors and cytokine signatures associated with the response to therapy in patients with primary biliary cholangitis-autoimmune hepatitis overlap syndrome: a real-world study.

Factors and cytokine signatures associated with the response to therapy in patients with primary biliary cholangitis-autoimmune hepatitis overlap syndrome: a real-world study.

Serum Interleukin-37 Levels in Patients with Systemic Sclerosis and its Relation with Clinical Findings

Aim: This study investigates serum interleukin(IL)-37 levels in patients with systemic sclerosis (SS) and assesses its relationship with clinical findings.&#x0D; Methods: This study included 35 patients with SS and 30 healthy control subjects. The demographic and clinical characteristics of the patients, such as the presence of Raynaud’s phenomenon, SS subtype, digital ulcers, gastrointestinal and lung involvement, and disease activity, were recorded. The medications used by the patients were recorded, and Serum IL-37 levels were measured using an enzyme-linked immunosorbent assay. The United Kingdom Functional Scoring system was used to evaluate the functional status of the patients, while the Valentini criteria were used to evaluate disease activity. Skin involvement was evaluated based on the modified Rodnan skin score.&#x0D; Results: Although serum IL-37 levels were found to be lower in patients with SS than in the control group, the difference was not statistically significant (p= 0.078). A negative correlation was identified between serum IL-37 levels and C3 levels in patients with SS (p= 0.046). No significant relationship was found between IL-37 levels and other clinical and laboratory parameters.&#x0D; Conclusion: Unlike in patients with autoimmune disorders, serum IL-37 levels were found to be lower in patients with SS than in the control subjects, and IL-37 demonstrated a negative correlation with C3 levels.

Correlation between clinical efficacy on pruritus and serum interleukin-31 levels in dogs with atopic dermatitis treated with lokivetmab.

Studies on serum interleukin (IL)-31 levels in dogs with atopic dermatitis (AD) and their correlation with disease severity are limited. To the author's knowledge, there are no studies that measured serum IL-31 in dogs treated with lokivetmab injections, a selective inhibitor of this key cytokine in pruritus. The aim of the study was to evaluate serum IL-31 levels in dogs treated with lokivetmab and correlate it with the severity of canine atopic dermatitis using the pruritus visual analog scale (pVAS) and canine atopic dermatitis extent and severity index (CADESI-04). Ten client-owned dogs diagnosed with AD received two injections of lokivetmab four weeks apart. Disease severity was assessed using the pVAS and CADESI-04 scores before and after both injections. In addition, canine serum IL-31 levels were measured at the same moments. Serum IL-31 was detected in all dogs in the study. There was a significant reduction in pVAS scores and serum IL-31 after administrations. However, there was no difference in CADESI-04 scores, and there was no significant correlation between CADESI-04 scores and serum IL-31 in dogs diagnosed with AD. Nonetheless, a significant positive correlation was observed between the pVAS scores and serum IL-31 levels with lokivetmab therapy, which reinforces the role of IL-31 in the pathogenesis of pruritus in dogs with AD. The data presented here provide further evidence that IL-31 is directly involved in pruritus pathogenesis in dogs with AD. In addition, blocking IL-31 has a significant antipruritic effect, but has no influence on skin lesion severity and extension.