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.

Low serum interleukin-38 levels in patients with Graves' disease and Hashimoto's thyroiditis.

BACKGROUND: Autoimmune thyroid disease (AITD) mainly includes Graves' disease (GD) and Hashimoto's thyroiditis (HT), which is caused by individual genetics, autoimmune dysfunction, and a variety of external environmental factors. Interleukin (IL)-38 is involved in a wide range of autoimmune diseases, but little is known about IL-38 expression in AITD. METHODS: Fifty patients with GD, 50 with HT, and 50 healthy controls (HC) were enrolled in this study. Basic information of the participants was obtained through a physical examination. Immunological data were obtained by an automatic chemiluminescence immunoanalyzer. C-reactive protein (CRP) concentrations and the white blood cell count were measured. Serum IL-38 levels were determined by an enzyme-linked immunosorbent assay. RESULTS: Serum IL-38 levels were significantly lower in the GD and HT groups than in the HC group (both p < 0.01). Serum CRP concentrations were significantly lower in the HT group than in the HC group (p < 0.05). Receiver operating characteristic curve analysis showed that the area under the curve was 0.7736 (p < 0.01) for IL-38 and 0.7972 (p < 0.01) for IL-38 combined with CRP in the GD group. In the HT group, the area under the curve was 0.7276 (p < 0.01) for IL-38 and 0.7300 for IL-38 combined with CRP (p < 0.01). CONCLUSIONS: The results suggest that serum IL-38 level is a potential new diagnostic biomarker in patients with GD and HT.

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.

Interleukin-39 exacerbates concanavalin A-induced liver injury.

BACKGROUND: Interleukin (IL)-39 is a novel member of IL-12 family and has been reported to play a pro-inflammatory role in lupus-like mice, but its function in concanavalin A (ConA)-induced liver injury is currently unclear. MATERIALS AND METHODS: In this study, we investigated the effects of IL-39 expression in a mouse model of ConA induced-hepatitis. We first showed that delivery of plasmid DNA encoding mouse IL-39 using the hydrodynamic tail vein injection method increased IL-39 mRNA and protein levels in the liver. We then administrated mice with IL-39 plasmid before ConA injection and measured serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, inflammatory infiltration, and hepatocyte necrosis in the liver. Additionally, we further explored the potential mechanism of IL-39 in ConA-induced liver injury by measuring several inflammatory mediators. RESULTS: We found that ectopic IL-39 expression promoted the ConA-induced increase in serum ALT and AST levels, inflammatory infiltration, and hepatocyte necrosis in the liver. We also observed that IL-39 plasmid administration significantly increased serum and liver interferon-γ, tumor necrosis factor-α, and IL-17A levels, but did not affect serum and liver IL-10 levels in ConA-induced hepatitis. CONCLUSION: Our results suggest that IL-39 can exacerbate ConA-induced hepatitis and may be a therapeutic target in inflammatory liver disease.

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.