The Clinical Significance of Serum Interleukin-36α Levels in Patients with Gout.

BACKGROUND: Gout is a chronic inflammatory diseases caused by monosodium urate crystal deposition. However, the role of interleukin (IL)-36 in gout has not dbeen elucidated. METHODS: We enrolled 75 subjects, including 20 healthy controls (HC), 30 patients with acute gout attack and 25 patients in remission. Baseline data were obtained through clinical interrogation and laboratory data were obtained through tests of blood samples. Serum levels of IL-36α were detected using enzyme-linked immunosorbent assay. Spearman correlation analysis was used to investigate the correlation of IL-36α with other parameters. The diagnostic value of IL-36α was demonstrated using a receiver operating characteristic curve. RESULTS: The serum IL-36α level of gout patients in acute attack and remission stage was significantly higher than that of HC. Serum IL-36α was positively correlated with alanine transaminase (ALT) and aspartate transaminase (AST). Serum amyloid A (SAA) levels positively correlated with C-reactive protein levels and erythrocyte sedimentation rates. Glutamyl transpeptidase levels positively correlated with AST and ALT levels. CONCLUSION: In conclusion, serum IL-36α levels were elevated in patients with gout and correlated with the clinical markers of inflammation. Our findings suggest that IL-36α may be a novel inflammatory indicator for gout.

Interleukin-41 as a biomarker of the anti-inflammatory response associated with hyperuricemia.

BACKGROUND: Interleukin (IL)-41 is a recently discovered secreted protein that is expressed in a variety of tissues, and it is associated with several immune and metabolic diseases. However, IL-41 has not been studied in hyperuricemia (HUA). METHODS: Forty-four HUA patients and 44 healthy controls (HCs) were included in this study, and we collected theirgeneral and biochemical parameters, including white blood cell, neutrophil, lymphocyte, and platelet counts, mean platelet volume, platelet distribution width, serum creatinine, blood urea nitrogen, fasting blood glucose, total triglyceride, total cholesterol, high-density lipoprotein, low-density lipoprotein, total protein, albumin, alkaline phosphatase, gamma-glutamyltransferase, and hemoglobin concentration. The level of serum IL-41 was determined using an enzyme-linked immunosorbent assay. Multivariate logistic regression analysis was exploited to identify the independent risk factors associated with HUA, and the clinical diagnostic value of IL-41 was analyzed by applying the receiver operating characteristic (ROC) curve. We assessed the association between IL-41 and clinical parameters with Spearman's rank correlation. RESULTS: Circulating IL-41 levels were significantly higher in HUA patients than in the HCs group (460.3 pg/mL vs. 261.3 pg/mL, respectively; P < 0.001). The area under the ROC curve (AUC) for IL-41 in HUA patients was 0.7443 (with a cut-off value of 311.055 pg/mL, a sensitivity of 68.18 %, and a specificity of 72.73 %), while the AUC for IL-41 combined with the platelet count was 0.8109. Correlation analysis revealed that the circulating IL-41 level was positively correlated with age in HCs and HUA patients. CONCLUSIONS: We herein demonstrated that serum IL-41 was elevated in HUA patients and that it may constitute a novel biomarker of anti-inflammatory response related to HUA.

Elevated serum IL-36γ levels in patients with ankylosing spondylitis and its association with disease activity.

Ankylosing spondylitis (AS) is a chronic autoimmune disease. The purpose of this study was to investigate the levels of serum IL-36γ in AS patients and their association with AS. The study enrolled 131 subjects, including 45 with active AS, 46 with inactive AS, and 40 healthy controls (HCs). The basic clinical information of each participant was obtained through physical examination and relevant clinical medical records. Serum IL-36γ levels were detected through an enzyme-linked immunosorbent assay. Serum IL-36γ levels in the active AS group were significantly higher than those in the HC group (94.72 vs. 65.76 pg/mL, P = 0.0087). The serum IL-36γ concentration in the inactive AS group was increased as compared to that in the HC group (100.90 vs. 65.76 pg/mL, P = 0.0138). Correlation analysis indicated that serum IL-36γ was positively correlated with glutamyl transferase in the active AS group (P = 0.0172), while serum IL-36γ was positively correlated with uric acid in the inactive AS group (P = 0.0151). The area under the curve (AUC) for IL-36γ was 0.6824 (P = 0.0009), and the AUC for IL-36γ combined with the erythrocyte sedimentation rate and C-reactive protein levels was 0.8102 (P < 0.0001), according to receiver operating characteristic curve analysis. This study found that serum IL-36γ levels were elevated in AS patients and correlated with disease activity. Our results suggest that IL-36γ may be involved in the progression of AS disease and is a potential biomarker for AS.

Interleukin-41 diminishes cigarette smoke-induced lung inflammation in mice.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) and other inflammatory lung illnesses are markedly exacerbated by cigarette smoke (CS). The novel cytokine interleukin (IL)-41 has immunoregulatory effects, but data on its function in lung inflammation caused by CS are limited and inconclusive. Our study aimed to investigate the ability of IL-41 to protect against CS-induced lung inflammation in vivo. METHODS: In this model, mice were exposed to six cigarettes three times daily for 1 h, with 4-hour intervals between exposures, for 5 consecutive days. Mice received an intraperitoneal dose of IL-41 or a negative control 1 day prior to their initial exposure to CS. On day 6, mice were sacrificed to assess the impact of IL-41 on CS-induced lung inflammation. RESULTS: We found that IL-41 pre-treatment alleviated pulmonary inflammatory infiltration and lung tissue lesions. IL-41 pre-treatment also limited CS-induced weight loss, and resulted in lower numbers of macrophages in the bronchoalveolar lavage fluid and lower percentages of neutrophils and monocytes in the blood. Furthermore, it promoted the polarization of M2 macrophages rather than M1 macrophages, as determined by immunohistochemistry. Consistent with its effects on M2 polarization, pre-treatment with IL-41 was associated with higher levels of IL-10 in the bronchoalveolar lavage fluid and lung tissues of CS-exposed animals and lower production of tumor necrosis factor-α, IL-6 and IL-1ß in the serum and lung tissues. CONCLUSIONS: These findings suggest that IL-41 could be used therapeutically to treat CS-induced lung inflammatory disorders as it inhibits CS-induced pulmonary inflammation when administered in vivo in mice.

Circulating interleukin-39 as a potential biomarker for rheumatoid arthritis diagnosis.

BACKGROUND: Imbalances in cytokine networks have been shown to be a possible cause of rheumatoid arthritis (RA). The interleukin (IL)-12 family is involved in the pathogenesis of autoimmune diseases including RA, while IL-39 is a newly discovered member of the IL-12 family, although its role in RA remains unclear. The purpose of the present study was to detect the expression of IL-39 in the sera of patients with RA and its relationship with RA activity. METHODS: We recruited 46 patients with RA and 35 healthy controls at Ningbo Sixth Hospital. Blood samples were collected for biochemical analysis, and disease activity scores of 28 joints based on C-reactive protein were monitored. Serum concentrations of IL-39 were determined using an enzyme-linked immunosorbent assay. The Pearson correlation test was used to analyze the association between serum IL-39 levels and clinical indicators. RESULTS: Serum levels of IL-39 were significantly higher in patients with RA compared with healthy controls (p < 0.0001). IL-39 levels positively correlated with rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), and IgM; RF positively correlated with ESR. Receiver operating characteristic curve analysis showed that IL-39 has diagnostic value for RA (p < 0.0001). CONCLUSIONS: The significant increase of IL-39 levels in serum of patients with RA and its positive correlation with clinical indicators suggest that IL-39 may serve as biomarker for the diagnosis of RA.

Potential clinical value of serum interleukin-41 levels in patients with acute gout.

BACKGROUND: Gout is a common metabolic rheumatic disease, and there have been no reports on the serum levels of interleukin (IL)-41 in gout patients. The purpose of this study was to therefore determine the expression of IL-41 in the serum of gout patients. METHODS: Eighty-one participants were enrolled in this study, including 34 patients with acute gout, 27 gout patients in remission, and 20 healthy controls (HCs). Baseline data were obtained through interviews and laboratory parameters were acquired via blood sample testing. We measured serum IL-41 concentrations with an enzyme-linked immunosorbent assay, and executed Spearman's correlation analysis to investigate the correlation between IL-41 and other parameters, and the diagnostic value for IL-41 was demonstrated using a receiver operating characteristic curve. Multivariate analysis was conducted by adopting logistic regression. RESULTS: Serum IL-41 concentrations in acute-gout patients were higher than those in HCs and there was no significant difference in serum IL-41 levels between remission gout patients and HCs. In addition, IL-41 was positively correlated with white blood cell count, erythrocyte sedimentation rate, and C-reactive protein and serum amyloid A concentrations, while it was negatively correlated with triglyceride levels. IL-41 showed good diagnostic value for gout, and the combination of IL-41 and uric acid produced a superior diagnostic value. We also noted that IL-41 was an independent risk factor for acute gout. CONCLUSIONS: This study revealed that serum IL-41 was elevated in patients with acute gout, and suggests that IL-41 may constitute a novel diagnostic marker for acute gout.

Clinical diagnostic value of serum soluble IL-2 receptor for stage I sarcoidosis in benign isolated mediastinal and hilar lymphadenopathy.

BACKGROUND: Serum soluble interleukin-2 receptor (sIL-2R) is recognized as a marker of T-cell activation and is abnormally elevated in sarcoidosis. However, its value for stage I sarcoidosis in benign granulomatous diseases is unclear. METHODS: We enrolled 33 stage I sarcoidosis patients, 17 lymph node tuberculosis patients, 15 reactive lymphadenopathy patients, and 11 healthy controls. Serum biomarkers concentrations were collected and collated. RESULTS: Serum sIL-2R concentrations were the highest in stage I sarcoidosis. The AUC of serum sIL-2R for stage I sarcoidosis was 0.7452 in all subjects and 0.6861 in granulomatous diseases. The AUCs of two combined diagnostic forms, sIL-2R with angiotensin-converting enzyme (ACE) and sIL-2R with ACE, erythrocyte sedimentation rate (ESR), and lactate dehydrogenase (LDH) were 0.7994 and 0.891 in all subjects, respectively. In granulomatous disease groups for ROC analysis, the best cut-off value of sIL-2R was 745.00 U/ml with 48.50% sensitivity and 84.40% specificity. The combination of four parameters increased the diagnostic accuracy for stage I sarcoidosis in granulomatous diseases (74.10% sensitivity and 100% specificity). Serum sIL-2R concentrations were positively correlated with serum ACE (r = 0.4652, P = 0.0126). CONCLUSION: Serum sIL-2R appeared to be valuable in identifying stage I sarcoidosis in a group of benign granulomatous disorders.

Serum interleukin-38 and -41 levels as candidate biomarkers in male infertility.

BACKGROUND: Interleukin (IL)-38 and IL-41 are novel cytokines, but their role in male infertility (MI) is unknown. The purpose of this study was to measure the levels of serum IL-38 and IL-41 in patients with MI and correlate these levels with semen indexes. METHODS: Eighty-two patients with MI and 45 healthy controls (HC) were recruited for this study. Semen parameters were detected using computer-aided sperm analysis, Papanicolaou staining, ELISA, flow cytometry, peroxidase staining and enzyme methods. Serum IL-38 and IL-41 levels were determined by ELISA. RESULTS: Serum IL-38 levels were decreased (P < 0.01) in patients with MI compared with HC. Serum IL-41 levels were significantly higher in patients with MI than in HC (P < 0.0001). In patients with MI, serum IL-38 levels were positively correlated with semen white blood cell counts (r = 0.29, P = 0.009), and there was a positive correlation between semen white blood cell counts and sperm concentration (r = 0.28, P = 0.0100) and seminal plasma elastase (r = 0.67, P < 0.0001). Receiver operating characteristic curve analysis showed that the area under the curve of IL-38 for diagnosing MI was 0.5637 (P > 0.05), and the area under the curve of IL-41 for diagnosing MI was 0.7646 (P < 0.0001). CONCLUSIONS: Serum IL-38 levels were significantly lower, and serum IL-41 levels were higher in patients with MI. These results suggest that IL-38 and IL-41 may be novel biomarkers for the diagnosis of MI.

Plasma interleukin-41 serves as a potential diagnostic biomarker for Kawasaki disease.

INTRODUCTION: Kawasaki disease (KD) is a systemic vasculitis that causes abnormalities in the coronary arteries. Interleukin (IL)-41 is a novel immunoregulatory cytokine involved in the pathogenesis of some inflammatory and immune-related diseases. However, the role of IL-41 in KD is unclear. The purpose of this study was to detect the expression of IL-41 in the plasma of children with KD and its relationship with the disease. METHODS: A total of 44 children with KD and 37 healthy controls (HC) were recruited for this study. Plasma concentrations of IL-41 were determined by ELISA. Correlations between plasma IL-41 levels and KD-related clinical parameters were analyzed by Pearson correlation and multivariate linear regression analysis. Receiver operating characteristic curve analysis was used to assess the clinical value of IL-41 in the diagnosis of KD. RESULTS: Our results showed that plasma IL-41 levels were significantly elevated in children with KD compared with HC. Correlation analysis demonstrated that IL-41 levels were positively correlated with D-dimer and N-terminal pro-B-type natriuretic peptide, and negatively correlated with IgM, mean corpuscular hemoglobin concentration, total protein, albumin and pre-albumin. Multivariable linear regression analysis revealed that IgM and mean corpuscular hemoglobin concentrations were associated with IL-41. Receiver operating characteristic curve analysis showed that the area under the curve of IL-41 was 0.7101, with IL-41 providing 88.64 % sensitivity and 54.05 % specificity. CONCLUSION: Our study indicated that plasma IL-41 levels in children with KD were significantly higher than those in HC, and may provide a potential diagnostic biomarker for KD.

Increased serum IL-41 is associated with disease activity in rheumatoid arthritis.

BACKGROUND: Interleukin (IL)-41 is upregulated in the synovial tissue of rheumatoid arthritis (RA) patients, but its serum level has not been reported. The present study aimed to determine IL-41 expression in serum from RA patients and to clarify the relationships between IL-41 and disease-related parameters in RA patients. METHODS: The study included 46 RA patients and 32 healthy controls (HC). Baseline data were obtained by routine physical examinations and immune-related parameters were measured by an automated chemiluminescent immunoassay analyzer. The correlations between IL-41 and disease activity score in 28 joints (DAS28) and serum clinical data were analyzed using the Pearson correlation test. RESULTS: Serum IL-41 concentrations were higher in RA patients than in HC. Serum IL-41 was positively correlated with DAS28 based on C-reactive protein (DAS28-CRP), CRP, erythrocyte sedimentation rate (ESR), mean platelet volume (MPV), and CRP-to-albumin ratio (CAR) and negatively correlated with platelet count, while rheumatoid factor was significantly correlated with ESR, CRP, and CAR. Receiver operating characteristic curve analysis showed that IL-41 had diagnostic value for RA, especially when combined with MPV. CONCLUSIONS: The present findings suggest that IL-41 is increased in the serum of RA patients and may be a potential new diagnostic biomarker for RA.

Clinical significance of elevated serum IL-36γ levels in patients with early-stage Hashimoto's thyroiditis.

OBJECTIVES: Hashimoto's thyroiditis (HT) is the predominant cause of primary hypothyroidism. Interleukin (IL)-36γ is a member of the IL-36 family. Recently, IL-36γ was shown to possess proinflammatory properties in autoimmune diseases. However, the role of IL-36γ in HT is insufficiently understood. The purpose of the present study was to investigate the potential relationship between IL-36γ and HT. DESIGN & METHODS: We included 100 subjects, among whom, 52 had early-stage HT and 48 were healthy controls (HC). The subjects' basic clinical information was obtained through physical examination and clinical histories of signs and symptoms. Thyroid function and measurements of thyroid-stimulating hormone (TSH), free triiodothyronine 3, free triiodothyronine 4 (FT4), thyroid peroxidase antibody (TPO-Ab), and thyroid globulin antibody were measured using a fully automated chemiluminescent immunoassay analyzer. The expression levels of serum IL-36γ were determined using an enzyme-linked immunosorbent assay. RESULTS: The serum IL-36γ level in the HT group was significantly higher compared with that of the HC group [91.91 (67.52, 130.90) pg/mL vs 62.50 (44.61, 91.53) pg/mL, P < 0.0001]. Correlation analysis showed a negative correlation between serum IL-36γ and TPO-Ab titers in the HT group (r = -0.3507, P = 0.0054). According to receiver operating characteristic curve analysis, the area under the curve (AUC) for IL-36γ was 0.7278 (P < 0.0001), and the AUC for IL-36γ combined with TSH and FT4 was 0.8109 (P < 0.0001). CONCLUSIONS: The present study indicates that serum IL-36γ expression is increased in patients with HT and negatively correlates with TPO-Ab. Our findings suggest that IL-36γ may be involved in the development of HT and may therefore serve as a potential new diagnostic biomarker for HT.

Serum IL-38 levels in patients with type 2 diabetes mellitus.

INTRODUCTION: Interleukin 38 (IL-38) is a new member of the IL-1 family, and it has anti-inflammatory activity. However, its role in type 2 diabetes mellitus (T2DM) has not been reported. MATERIAL AND METHODS: The study included 40 T2DM patients and 42 healthy control subjects. The anthropometric and biochemical measurements were performed using an automatic biochemical analyser, high-performance liquid chromatography, and electrochemiluminescence immunoassay. Circulating IL-38 levels were determined by enzyme-linked immunosorbent assay. RESULTS: Serum IL-38 levels in T2DM patients were significantly lower than those in controls. Correlation analysis showed that serum IL-38 was negatively correlated with systolic blood pressure and interleukin 17 (IL-17). CONCLUSIONS: The results suggest that IL-38 may be a new biomarker of T2DM.

Development and internal validation of a risk model for hyperuricemia in diabetic kidney disease patients.

Purpose: This research aimed to identify independent risk factors for hyperuricemia (HUA) in diabetic kidney disease (DKD) patients and develop an HUA risk model based on a retrospective study in Ningbo, China. Patients and methods: Six hundred and ten DKD patients attending the two hospitals between January 2019 and December 2020 were enrolled in this research and randomized to the training and validation cohorts based on the corresponding ratio (7:3). Independent risk factors associated with HUA were identified by multivariable logistic regression analysis. The characteristic variables of the HUA risk prediction model were screened out by the least absolute shrinkage and selection operator (LASSO) combined with 10-fold cross-validation, and the model was presented by nomogram. The C-index and receiver operating characteristic (ROC) curve, calibration curve and Hosmer-Lemeshow test, and decision curve analysis (DCA) were performed to evaluate the discriminatory power, degree of fitting, and clinical applicability of the risk model. Results: Body mass index (BMI), HbA1c, estimated glomerular filtration rate (eGFR), and hyperlipidemia were identified as independent risk factors for HUA in the DKD population. The characteristic variables (gender, family history of T2DM, drinking history, BMI, and hyperlipidemia) were screened out by LASSO combined with 10-fold cross-validation and included as predictors in the HUA risk prediction model. In the training cohort, the HUA risk model showed good discriminatory power with a C-index of 0.761 (95% CI: 0.712-0.810) and excellent degree of fit (Hosmer-Lemeshow test, P > 0.05), and the results of the DCA showed that the prediction model could be beneficial for patients when the threshold probability was 9-79%. Meanwhile, the risk model was also well validated in the validation cohort, where the C-index was 0.843 (95% CI: 0.780-0.906), the degree of fit was good, and the DCA risk threshold probability was 7-100%. Conclusion: The development of risk models contributes to the early identification and prevention of HUA in the DKD population, which is vital for preventing and reducing adverse prognostic events in DKD.

Interleukin-37 ameliorates cigarette smoke-induced lung inflammation in mice.

Cigarette smoking (CS) is the leading cause of chronic obstructive pulmonary disease, and its severity is closely related to lung inflammation. Interleukin (IL)-37 is a newly discovered member of the IL-1 family with anti-inflammatory activity. Our study aimed to elucidate the effect of IL-37 on CS-induced lung inflammation in mice. In this study, mice were exposed to six cigarettes for 1 h three times daily (4 h smoke-free intervals) for 10 consecutive days. Mice were treated intranasally with IL-37-expressing lentivirus and empty lentivirus particles 1 day before the first CS or sham exposure. Mice were sacrificed on day 11 to evaluate the effect of IL-37 on CS-induced pulmonary inflammation in mice. Administering IL-37-expressing lentivirus significantly reduced CS-induced weight loss in mice compared to empty lentivirus controls (P < 0.05). Histological analysis showed that IL-37 significantly alleviated inflammatory cell recruitment, alveolar septum enlargement, alveolar wall attenuation, mucus hypersecretion, and goblet cell metaplasia in mouse lungs (P < 0.001). IL-37 expression also significantly inhibited CS-induced increases in inflammatory cells (including lymphocytes, neutrophils, and macrophages) in mouse lungs (P < 0.05), as well as pro-inflammatory cytokines such as IL-1ß, IL-6, IL-17, monocyte chemotactic protein-1 and tumor necrosis factor-α production (P < 0.05). IL-37 also significantly reduced myeloperoxidase activity in mouse serum (P < 0.01) and lung tissues (P < 0.001). Therefore, IL-37 can ameliorate CS-induced pulmonary inflammation in mice and IL-37 may be a potential therapeutic strategy for CS-induced lung inflammatory diseases.

Decreased serum interleukin-41/Metrnl levels in patients with Graves' disease.

BACKGROUND: Interleukin (IL)-41, also known as Metrnl, is a novel immunomodulatory cytokine, which is involved in the pathogenesis of many inflammatory and metabolic diseases, but its role in thyroid autoimmune diseases is not clear. The aim of this study was to evaluate the serum IL-41 levels in patients with Graves' disease (GD) and its relationship with GD. METHODS: This study included a total of 49 GD patients and 47 age- and sex-matched healthy individuals. All baseline data were obtained by physical examination. Free triiodothyronine 3 (FT3), free triiodothyronine 4 (FT4), thyroid-stimulating hormone (TSH), anti-thyroglobulin antibodies (TgAb), thyroid peroxidase antibody (TPOAb), and thyrotropin receptor antibody (TRAb) levels in plasma of GD patients were measured by chemiluminescence. The high-sensitivity C-reactive protein (CRP) and white blood cell count (WBC) were detected using automated biochemical analyzer. Serum IL-41 levels were measured by enzyme-linked immunosorbent assay. RESULTS: Serum IL-41 levels in patients with GD were significantly lower than those in healthy controls (201.0 vs. 260.8 pg/mL, p < 0.05). There was a significant positive correlation between IL-41 level and CRP (r = 0.2947, p = 0.0385) and WBC (r = 0.4104, p = 0.0034) in GD patients. CRP was positively correlated with TRAb (r = 0.2874, p = 0.0452) and TSH (r = 0.3651, p = 0.0099) levels in GD patients. CONCLUSIONS: This study demonstrates that GD patients have decreased serum IL-41 levels, and IL-41 plays a potential role in abnormal immune response of GD patients.

The potential value of low-level serum interleukin-38 for the clinical diagnosis and risk prediction of hyperuricemia.

BACKGROUND: Interleukin (IL)-38, a novel anti-inflammatory cytokine in the IL-1 family, has an important role in various autoimmune/inflammatory diseases. However, the level of serum IL-38 in hyperuricemia (HUA) and its clinical applications are still unknown. METHODS: Forty-four HUA patients and 43 healthy controls were enrolled in this study. The levels of serum IL-38 in the participants were detected by enzyme-linked immunosorbent assay. Multivariable logistic regression analysis was used to identify independent risk factors associated with HUA. The least absolute shrinkage and selection operator combined with 10-fold cross-validation was used to screen the characteristic variables for modeling and the logistic regression model was visualized by nomogram. The discrimination, degree of concordance, and clinical applicability of the models were evaluated by receiver operator characteristic curve, calibration plot, and decision curve analysis, respectively. RESULTS: Compared with that in healthy controls, the level of serum IL-38 was reduced in HUA patients (275.09 ± 294.89 vs 505.99 ± 312.94, P < 0.01). The area under the curve of serum IL-38 was 0.768 (cutoff value: 246.91 pg/ml). IL-38, platelet count, mean platelet volume, and total protein were identified as independent risk factors for HUA. The risk model showed an excellent clinical differentiation value (area under the curve: 0.961) and degree of fit. Decision curve analysis indicated that the prediction model could be beneficial for patients when the threshold probability was 1%-95%. CONCLUSIONS: Low level of serum IL-38 shows some potential in the clinical diagnosis and risk prediction of HUA. In addition, as a novel biomarker of HUA, serum IL-38 would contribute to the in-depth study of its pathogenesis in the future.

Metabolomics: A New Tool to Reveal the Nature of Diabetic Kidney Disease.

Metabolomics is a field of systems biology that draws on the scientific methods of other groups to qualitatively or quantitatively characterize small molecule metabolites in organisms, revealing their interconnections with the state of the organism at an overall relative macroscopic level. Diabetic kidney disease (DKD) is well known as a chronic metabolic disease, and metabolomics provides an excellent platform for its clinical study. A growing number of metabolomic analyses have revealed that individuals with DKD have metabolic disturbances of multiple substances in their bodies. With the continuous development and improvement of metabolomic analysis technology, the application of metabolomics in the clinical research of DKD is also expanding. This review discusses the recent progress of metabolomics in the early diagnosis, disease prognosis, and pathogenesis of DKD at the level of small molecule metabolites in vivo.

Protective Effects of Interleukin-37 Expression against Acetaminophen-Induced Hepatotoxicity in Mice.

Aim: Interleukin (IL)-37 is a new anti-inflammatory cytokine of the IL-1 family. This study aimed to determine the effects of IL-37 on acetaminophen (APAP)-induced liver injury. Materials and Methods: IL-37 plasmids were injected into mice via a tail vein hydrodynamics-based gene delivery. Results: Our results showed that IL-37 pretreatment significantly decreased serum alanine aminotransferase and aspartate aminotransferase levels, hepatic myeloperoxidase activity, and attenuated the histological liver damage. Compared to the APAP group, IL-37 administration decreased Kupffer cells numbers in the liver of APAP-induced hepatotoxicity in mice. Furthermore, IL-37 pretreatment reduced the expression of proinflammatory cytokines including tumor necrosis factor-α, IL-6, IL-17, and nuclear factor-κB (NF-κB) in APAP-induced mice. Conclusion: These results demonstrate that delivery of IL-37 plasmid can ameliorate APAP-induced liver injury by reducing proinflammatory cytokines production and preventing the activation of the NF-κB signaling pathway. IL-37 may be a promising candidate against APAP-induced liver injury.

Low levels of serum IL-39 are associated with autoimmune thyroid disease.

BACKGROUND: Interleukin (IL)-39 is a novel member of IL-12 cytokine family, but its role in autoimmune thyroid diseases (AITD) is unclear. The aim of the present study was to determine serum levels of IL-39 in Hashimoto's thyroiditis (HT) and Graves' disease (GD) patients. METHODS: A total of 48 patients with HT, 50 patients with GD, and 45 healthy controls (HCs) were recruited for this study. Levels of serum IL-39 were determined by ELISA. RESULTS: Compared with HC group, levels of serum IL-39 in patients with HT (p < 0.05) and GD (p < 0.01) were drastically reduced. Among patients with HT, serum IL-39 levels had a positive correlation with white blood cell count (WBC) count and free triiodothyronine level. Among patients with GD, the levels of IL-39 in serum were positively correlated with WBC count and C-reactive protein levels. CONCLUSIONS: IL-39 may be a new potential predictor for patients with HT and GD.

Serum IL-36 cytokines levels in idiopathic pulmonary fibrosis and connective tissue disease-associated interstitial lung diseases.

BACKGROUND: Interleukin-36 (IL-36) family is associated with several fibrosis-related disorders and connective tissue diseases. However, their expression in idiopathic pulmonary fibrosis (IPF) and connective tissue disease-interstitial lung disease (CTD-ILD) is unknown. METHODS: We included 19 CTD-ILD patients, 16 IPF patients, and 27 healthy control subjects. Determination of serum concentrations of IL-36α, IL-36γ and IL-36 receptor antagonist (IL-36Ra) was performed by ELISA. The value of biomarkers for the diagnosis and assessment of ILD was assessed by lung function tests and high-resolution computed tomography. RESULTS: Serum concentrations of IL-36α and IL-36γ in patients with CTD-ILD and IPF were significantly higher than that in healthy controls, whereas serum IL-36Ra concentrations were not significantly different between the 3 groups. Increased IL-36 levels correlated with disease severity in IPF patients. ROC curve analysis showed that the AUC was 0.9931 for IL-36α and 0.8194 for IL-36γ in IPF group. In CTD-ILD group, the AUC was 0.9825 for IL-36α and 0.7973 for IL-36γ. CONCLUSIONS: We demonstrated an imbalance in the agonist and antagonist profiles of IL-36 cytokines in ILD. IL-36 cytokines may be a new diagnostic or therapeutic target in ILD, especially in IPF.