IL-1 receptor antagonist-mediated therapeutic effect in murine myasthenia gravis is associated with suppressed serum proinflammatory cytokines, C3, and anti-acetylcholine receptor IgG1

In myasthenia gravis (MG), TNF and IL-1beta polymorphisms and high serum levels of these proinflammatory cytokines have been observed. Likewise, TNF and IL-1beta are critical for the activation of acetylcholine receptor (AChR)-specific T and B cells and for the development of experimental autoimmune myasthenia gravis (EAMG) induced by AChR immunization. We tested the therapeutic effect of human recombinant IL-1 receptor antagonist (IL-1ra) in C57BL/6 mice with EAMG. Multiple daily injections of 0.01 mg of IL-1ra administered for 2 wk following two AChR immunizations decreased the incidence and severity of clinical EAMG. Furthermore, IL-1ra treatment of mice with ongoing clinical EAMG reduced the clinical symptoms of disease. The IL-1ra-mediated suppression of clinical disease was associated with suppressed serum IFN-gamma, TNF-alpha, IL-1beta, IL-2, IL-6, C3, and anti-AChR IgG1 without influencing total serum IgG. Therefore, IL-1ra could be used as a nonsteroidal drug for the treatment of MG.     

血清IL-6、miR-17-5p水平与卵巢癌患者化疗后生存期的相关性分析

目的:分析血清白细胞介素-6(IL-6)、微小RNA-17-5p(miR-17-5p)水平与卵巢癌患者化疗后生存期的相关性。方法:选取行手术治疗联合术后化疗的65例卵巢癌患者作为病例组,选取50名健康体检者作为对照组,选取50例良性卵巢疾病患者作为良性疾病组,对病例组患者术前及术后14d的血清IL-6、miR-17-5p水平进行检测和比较,对良性疾病组和对照组研究对象的血清IL-6、miR-17-5p水平进行检测和比较,对病例组患者进行随访,对其总生存期(OS)和无疾病进展生存期(PFS)进行观察和比较。结果:病例组患者血清IL-6、miR-17-5p表达水平显著高于良性疾病组,良性疾病组患者的血清IL-6、miR-17-5p表达水平显著高于对照组,各组之间的差异均有统计学意义(P0.05)。病例组患者术后14d血清IL-6、miR-17-5p表达水平较手术前显著下降,差异均有统计学意义(P0.05)。血清IL-6、miR-17-5p高表达的卵巢癌患者中TNM分期为Ⅲ~Ⅳ期的比例较高,差异均有统计学意义(P0.05)。血清IL-6、miR-17-5p高表达卵巢癌患者的OS和PFS明显短于血清IL-6、miR-17-5p低表达患者,差异均有统计学意义(P0.05)。血清IL-6和miR-17-5p同时呈现低表达的卵巢癌患者的OS和PFS水平最高,血清IL-6或miR-17-5p其中之一呈现高表达卵巢癌患者的OS和PFS水平居中,而血清IL-6和miR-17-5p同时呈现高表达的OS和PFS水平最低,差异均有统计学意义(P0.05)。结论:卵巢癌患者可表现为血清IL-6、miR-17-5p水平的显著升高,在手术治疗后,其水平会出现下降,术前较高的血清IL-6、miR-17-5p表达水平与较短的生存期和不良预后具有关联性,可作为预测患者预后的辅助指标。     

MicroRNA-125b protects liver from ischemia/reperfusion injury via inhibiting TRAF6 and NF-κB pathway

MicroRNA-125b (miR-125b), which was previously proved to be a potential immunomodulator in various disease, attenuated mouse hepatic ischemia/reperfusion (I/R) injury in this study. miR-125b was decreased in RAW 264.7 cells exposed to hypoxia/reoxygenation (H/R). The expression of IL-1β, IL-6 and TNF-α in both serum and supernate were reduced in miR-125b over-expression groups. The hepatic histopathological changes were reduced in miR-125b agomir groups. In the miR-125b antagomir groups, serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were significantly elevated compared with negative control (NC) groups. The protein expression of TNF receptor-associated factor 6 (TRAF6), IL-1β and the phosphorylation of p65 (p-p65) were suppressed by the up-regulation of miR-125b. Furthermore, the nuclear translocation of p-p65, measured by immunofluorescence, was enhanced by the miR-125b inhibitors. In conclusion, our study indicates that miR-125b protects liver from hepatic I/R injury via inhibiting TRAF6 and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signal pathway.     

Aberrant Methylation of miR-34b and IL-12B mRNA Promoters Contributes to the Reduced Severity of Ankylosing Spondylitis

DNA methylation of Interleukin-12B (IL-12B) and miR-34b was proved to affect the expression of IL-12B and miR-34b, which were found to be involved in the pathogenesis of ankylosing spondylitis (AS). However, the molecular mechanisms underlying the role of IL-12B and miR-34b in AS remain to be explored. AS patients were divided into four groups according to their status of DNA methylation of miR-34b and IL-12B by bisulfite sequencing: HYPER-miR-34b?+?HYPO-IL-12B, HYPER-miR-34b?+?HYPER-IL-12B, HYPO-miR-34b?+?HYPER-IL-12B and HYPO-miR-34b?+?HYPO-IL-12B groups. Functional indicators were examined for patients with different status of DNA methylation in their miR-34b and IL-12B promoters. QPCR was performed to examine the expression of miR-34b and IL-12B mRNA under different conditions. ELISA was used to measure the expression of IL-12B p40 in the peripheral blood. Western blot was used to analyze the expression of IL-12B proteins. Luciferase assay was carried out to explore the suppressive role of miR-34b in IL-12B expression. The level of Ankylosing Spondylitis Disease Activity Score with C-reactive protein (ASDAS-CRP) was gradually increased in HYPER-miR-34b?+?HYPO-IL-12B,HYPER-miR-34b?+?HYPER-IL-12B,HYPO-miR-34b?+?HYPER-IL-12B and HYPO-miR-34b?+?HYPO-IL-12B groups, whereas the levels of Bath Ankylosing Spondylitis Functional Index (BASFI) and Bath Ankylosing Spondylitis Metrology Index (BASMI) were significantly elevated in the HYPO-miR-34b?+?HYPO-IL-12B group and diminished in the HYPER-miR-34b?+?HYPO-IL-12B group. The expression of miR-34b in the PBMCs and peripheral blood was remarkably higher in the HYPER-miR-34b?+?HYPO-IL-12B and HYPER-miR-34b?+?HYPER-IL-12B groups, whereas the expression of IL-12B was gradually decreased in the HYPER-miR-34b?+?HYPO-IL-12B, HYPER-miR-34b?+?HYPER-IL-12B, HYPO-miR-34b?+?HYPER-IL-12B and HYPO-miR-34b?+?HYPO-IL-12B groups. Luciferase assays with the transfection of miR-34b precursors suggested that miR-34b strongly suppressed the expression of IL-12B in THP-1 cells. In conclusion, our study demonstrated that hypermethylated miR-34b promoter led to evident upregulation of miR-34b, thus inhibiting the expression of IL-12B and alleviated the severity of ankylosing spondylitis by reducing the levels of factors including ASDAS-CRP, BASFI and BASMI.

     

MiR-522-3p inhibits proliferation and activation by regulating the expression of SLC31A1 in T cells

We investigated the role of miR-522-3p in thymoma-associated myasthenia gravis (TAMG), and the mechanism of action in T cells. The miR-522-3p expression in normal serum, non-thymoma MG patient serum and TAMG patient serum and tissues was detected by quantitative real-time PCR (qRT-PCR), respectively. We assessed miR-522-3p expression in Jurkat cells and human CD4⁺ T cells after activation by anti-CD3 and anti-CD28 using qRT-PCR. The viability, proliferation, cycle distribution and the levels of CD25, CD69, interleukin-2 (IL-2) and IL-10 in transfected Jurkat cells were detected by Cell counting kit-8, 5-ethynyl-2′-deoxyuridine (EdU), flow cytometry, qRT-PCR, respectively. Targeting relationships of miR-522-3p and SLC31A1 were predicted and validated by bioinformatics analysis and dual-luciferase reporter. The viability, proliferation, cycle distribution and the levels of SLC31A1, CD25, CD69, IL-2 and IL-10 in transfected Jurkat cells were detected by above methods and western blot. The miR-522-3p expression was declined in TAMG and activated T cells. MiR-522-3p inhibitor promoted cell viability, EdU positive cells, cycle progression, and the level of CD25, CD69, IL-2 and IL-10 in Jurkat cells, while the effect of miR-522-3p mimic was the opposite. SLC31A1 was targeted by miR-522-3p, and miR-522-3p inhibited SLC31A1 expression. Overexpressed SLC31A1 reversed the inhibitory effects of miR-522-3p mimic on cell viability, EdU positive cell, cycle progression, and the levels of IL-2 and IL-10 in transfected Jurkat cells. MiR-522-3p expression was down-regulated in TAMG, and miR-522-3p inhibited proliferation and activation by regulating SLC31A1 expression in T cells.

     

TLR3-Induced Placental miR-210 Down-Regulates the STAT6/Interleukin-4 Pathway

Several clinical studies have reported increased placental miR-210 expression in women with PE compared to normotensive women, but whether miR-210 plays a role in the etiology of PE is unknown. We reported that activation of TLR3 produces the PE-like symptoms of hypertension, endothelial dysfunction, and proteinuria in mice only when pregnant, but whether TLR3 activation in pregnant mice and human cytotrophoblasts (CTBs) increases miR-210 and modulates its targets related to inflammation are unknown. Placental miR-210 levels were increased significantly in pregnant mice treated with the TLR3 agonist poly I:C (P-PIC). Both HIF-1α and NF-κBp50, known to bind the miR-210 promoter and induce its expression, were also increased significantly in placentas of P-PIC mice. Target identification algorithms and gene ontology predicted STAT6 as an inflammation-related target of miR-210 and STAT6 was decreased significantly in placentas of P-PIC mice. IL-4, which is regulated by STAT6 and increases during normotensive pregnancy, failed to increase in serum of P-PIC mice. P-PIC TLR3 KO mice did not develop hypertension and placental HIF-1α, NF-κBp50, miR-210, STAT6, and IL-4 levels were unchanged. To determine the placental etiology, treatment of human CTBs with poly I:C significantly increased HIF-1α, NF-κBp50, and miR-210 levels and decreased STAT6 and IL-4 levels. Overexpression of miR-210 in CTBs decreased STAT6 and IL-4 while inhibition of miR-210 increased STAT6 and IL-4. These findings demonstrate that TLR3 activation induces placental miR-210 via HIF-1α and NF-κBp50 leading to decreased STAT6 and IL-4 levels and this may contribute to the development of PE.     

miR-200s Contribute to Interleukin-6 (IL-6)-induced Insulin Resistance in Hepatocytes

By influencing the activity of the PI3K/AKT pathway, IL-6 acts as an important regulator of hepatic insulin resistance. miR-200s have been shown to control growth by regulating PI3K, but the role of miR-200s in the development of hepatic insulin resistance remains unclear. The present study showed that elevated serum concentration of IL-6 is associated with decreased levels of miR-200s, impaired activation of the AKT/glycogen synthase kinase (GSK) pathway, and reduced glycogenesis that occurred in the livers of db/db mice. As shown in the murine NCTC 1469 hepatocytes and the primary hepatocytes treated with 10 ng/ml IL-6 for 24 h and in 12-week-old male C57BL/6J mice injected with 16 μg/ml IL-6 by pumps for 7 days, IL-6 administration induced insulin resistance through down-regulation of miR-200s. Moreover, IL-6 treatment inhibited the phosphorylation of AKT and GSK and decreased the glycogenesis. The effects of IL-6 could be diminished by suppression of FOG2 expression. We concluded that IL-6 treatment may impair the activities of the PI3K/AKT/GSK pathway and inhibit the synthesis of glycogen, perhaps via down-regulating miR-200s while augmenting FOG2 expression.     

The inhibiting effect of glucosamine sulfate combined with loxoprofen sodium on chondrocyte apoptosis in rats with knee osteoarthritis

Objectives:To explore the efficacy of glucosamine sulfate (GS) combined with loxoprofen sodium (LS) in rats with knee osteoarthritis (KOA) and its effect on chondrocytes.Methods:We randomly assigned 40 SPF SD rats to normal group (NG), control group (CG), treatment group (TG), and model group (MG). CG and TG were processed with continuous irrigation of LS and GS. NG and MG were given normal saline. We collected 3 mL of venous blood from the rat’s lower limb for the detection of serum IL-1β, IL-6, IL-8, and TNF-α by ELISA. Four weeks after irrigation, 5 rats in each group were randomly selected for anesthesia. The water content was detected, and the chondrocytes were collected. MTT assay was used to detect apoptosis, and Western blot (WB) to measure concentrations of Bax, Bcl-2, Caspase3, Caspase9, TLR4, and NF-kB.Results:The levels of IL-1 β, IL-6, IL-8, and TNF-α decreased in CG and TG, but increased in MG (P<0.05). After treatment, the expression of inflammatory factors was highest in MG (P<0.05).Conclusions:GS combined with LS showed good efficacy in rats with knee osteoarthritis, which may be achieved by inhibiting the expression of inflammatory factors and knee chondrocyte apoptosis via the TLR4-NF-kB pathway.     

Overexpression of microRNA-155 increases IL-21 mediated STAT3 signaling and IL-21 production in systemic lupus erythematosus

IntroductionInterleukin (IL)-21 is a key cytokine in autoimmune diseases such as systemic lupus erythematosus (SLE) by its regulation of autoantibody production and inflammatory responses. The objective of this study is to investigate the signaling capacity of IL-21 in T and B cells and assess its possible regulation by microRNA (miR)-155 and its target gene suppressor of cytokine signaling 1 (SOCS1) in SLE.MethodsThe signaling capacity of IL-21 was quantified by stimulating peripheral blood mononuclear cells (PBMCs) with IL-21 and measuring phosphorylation of STAT3 (pSTAT3) in CD4+ T cells, B cells, and natural killer cells. Induction of miR-155 by IL-21 was investigated by stimulating purified CD4+ T cells with IL-21 and measuring miR-155 expression levels. The functional role of miR-155 was assessed by overexpressing miR-155 in PBMCs from SLE patients and healthy controls (HCs) and measuring its effects on STAT3 and IL-21 production in CD4+ and CD8+ T cells.ResultsInduction of pSTAT3 in CD4+ T cells in response to IL-21 was significantly decreased in SLE patients compared to HCs (p < 0.0001). Further, expression levels of miR-155 were significantly decreased and SOCS1 correspondingly increased in CD4+ T cells from SLE patients. Finally, overexpression of miR-155 in CD4+ T cells increased STAT3 phosphorylation in response to IL-21 treatment (p < 0.01) and differentially increased IL-21 production in SLE patients compared to HCs (p < 0.01).ConclusionWe demonstrate that SLE patients have reduced IL-21 signaling capacity, decreased miR-155 levels, and increased SOCS1 levels compared to HCs. The reduced IL-21 signaling in SLE could be rescued by overexpression of miR-155, suggesting an important role for miR-155 in the reduced IL-21 signaling observed in SLE.

Electronic supplementary material

The online version of this article (doi:10.1186/s13075-015-0660-z) contains supplementary material, which is available to authorized users.     

Microbiota downregulates dendritic cell expression of miR-10a, which targets IL-12/IL-23p40

Commensal flora plays important roles in the regulation of the gene expression involved in many intestinal functions and the maintenance of immune homeostasis, as well as in the pathogenesis of inflammatory bowel diseases. The microRNAs (miRNAs), a class of small, noncoding RNAs, act as key regulators in many biological processes. The miRNAs are highly conserved among species and appear to play important roles in both innate and adaptive immunity, as they can control the differentiation of various immune cells, as well as their functions. However, it is still largely unknown how microbiota regulates miRNA expression, thereby contributing to intestinal homeostasis and pathogenesis of inflammatory bowel disease. In our current study, we found that microbiota negatively regulated intestinal miR-10a expression, because the intestines, as well as intestinal epithelial cells and dendritic cells of specific pathogen-free mice, expressed much lower levels of miR-10a compared with those in germ-free mice. Commensal bacteria downregulated dendritic cell miR-10a expression via TLR-TLR ligand interactions through a MyD88-dependent pathway. We identified IL-12/IL-23p40, a key molecule for innate immune responses to commensal bacteria, as a target of miR-10a. The ectopic expression of the miR-10a precursor inhibited, whereas the miR-10a inhibitor promoted, the expression of IL-12/IL-23p40 in dendritic cells. Mice with colitis expressing higher levels of IL-12/IL-23p40 exhibited lower levels of intestinal miR-10a compared with control mice. Collectively, our data demonstrated that microbiota negatively regulates host miR-10a expression, which may contribute to the maintenance of intestinal homeostasis by targeting IL-12/IL-23p40 expression.     

甲状腺癌患者血清IL-17、IL-35、SIL-2R表达水平及其临床意义

目的:探讨甲状腺癌患者血清白细胞介素-17(IL-17)、白细胞介素-35(IL-35)及可溶性白介素-2受体(SIL-2R)水平及其对甲状腺癌诊断与病情评估的临床价值。方法:选取我院2015年6月~2016年12月收治的甲状腺腺瘤患者38例、甲状腺癌患者49例为研究对象,另选取同期于我院体检中心接受体检的52例健康体检者为对照组。采用酶联免疫吸附法(ELISA)检测和比较其血清IL-17、IL-35、SIL-2R水平,并分析甲状腺癌患者血清IL-17、IL-35、SIL-2R水平与其年龄、病程、病理分期的相关性。结果:甲状腺腺瘤组血清IL-17、IL-35、SIL-2R水平与对照组比较差异均无统计学意义(P0.05)。甲状腺癌组血清IL-35水平显著低于甲状腺腺瘤组和对照组(P0.01),血清IL-17、SIL-2R水平均显著高于甲状腺瘤组和对照组(P0.01)。血清IL-17、SIL-2R水平随甲状腺癌分化程度的降低而升高,血清IL-35水平随甲状腺癌分化程度的降低而降低(P0.01)。血清IL-17、SIL-2R水平随甲状腺癌病理分期的增加而升高,血清IL-35水平随甲状腺癌病理分期的增加而降低(P0.01)。血清IL-17、SIL-2R水平与甲状腺癌病理分期均呈显著正相关(r=0.432、0.439,P均0.05)。血清IL-35水平与甲状腺癌病理分期呈显著负相关(r=-0.602,P0.05)。血清IL-17与IL-35呈显著负相关(r=-0.323,P0.05),IL-17与SIL-2R呈显著正相关(r=0.429,P0.05),IL-35与SIL-2R呈显著负相关(r=-0.415,P0.05)。结论:甲状腺癌患者的血清IL-17、SIL-2R水平均显著上调,IL-35水平显著下调,其对甲状腺癌的早期诊断、病情评估均具有重要参考价值。     

Differential Effects of IL-12 on Tregs and Non-Treg T Cells: Roles of IFN-γ, IL-2 and IL-2R

Complex interactions between effector T cells and Foxp3⁺ regulatory T cells (Treg) contribute to clinical outcomes in cancer, and autoimmune and infectious diseases. Previous work showed that IL-12 reversed Treg-mediated suppression of CD4⁺Foxp3⁻ T cell (Tconv) proliferation. We and others have also shown that Tregs express T-bet and IFN-γ at sites of Th1 inflammation and that IL-12 induces IFN-γ production by Tregs in vitro. To investigate whether loss of immunosuppression occurs when IFN-γ is expressed by Tregs we treated mouse lymphocyte cultures with IL-12. IFN-γ expression did not decrease the ability of Tregs to suppress Tconv proliferation. Rather, IL-12 treatment decreased Treg frequency and Foxp3 levels in Tregs. We further showed that IL-12 increased IL-2R expression on Tconv and CD8 T cells, diminished its expression on Tregs and decreased IL-2 production by Tconv and CD8 T cells. Together, these IL-12 mediated changes favored the outgrowth of non-Tregs. Additionally, we showed that treatment with a second cytokine, IL-27, decreased IL-2 expression without augmenting Tconv and CD8 T cell proliferation. Notably, IL-27 only slightly modified levels of IL-2R on non-Treg T cells. Together, these results show that IL-12 has multiple effects that modify the balance between Tregs and non-Tregs and support an important role for relative levels of IL-2R but not for IFN-γ expression in IL-12-mediated reversal of Treg immunosuppression.     

Protective role of estrogen-induced miRNA-29 expression in carbon tetrachloride-induced mouse liver injury

Previous studies have indicated that female animals are more resistant to carbon tetrachloride (CCl(4))-induced liver fibrosis than male animals, and that estradiol (E(2)) treatment can inhibit CCl(4)-induced animal hepatic fibrosis. The underlying mechanism governing these phenomena, however, has not been fully elucidated. Here we reported the role of estrogen-induced miRNA-29 (miR-29) expression in CCl(4)-induced mouse liver injury. Hepatic miR-29 levels were differentially regulated in female and male mice during CCl(4) treatment. Specifically, the levels of miR-29a and miR-29b expression were significantly decreased in the livers of male, but not female, mice following 4 weeks of CCl(4) treatment. The down-regulation of miR-29a and miR-29b in male mouse livers correlated with the early development of liver fibrosis, as indicated by increased expressions of fibrotic markers in male mice relative to female mice. In addition, E(2) was maintained at a higher level in female mice than in male mice. In contrast to TGF-β1 that decreased miR-29a/b expression in murine hepatoma IAR20 cells and normal hepatocytes, E(2) enhanced the expression of miR-29a/b through suppression of the nuclear factor-κB (NF-κB) signal pathway, which negatively regulates miR-29 expression. Furthermore, both E(2) treatment and intravenous injection of the recombinant adenovirus expressing miR-29a/b markedly increased the miR-29a/b level and attenuated the expression of fibrotic markers in mouse livers during CCl(4) treatment, supporting the protective role of E(2)-induced miR-29 in CCl(4)-induced hepatic injury. In conclusion, our results collectively demonstrate that estrogen can inhibit CCl(4)-induced hepatic injury through the induction of hepatic miR-29.     

Serum levels of TNF-alpha, IFN-gamma, IL-6, IL-8, IL-12, IL-17, and IL-18 in patients with active psoriasis and correlation with disease severity

Recent progress in the understanding of psoriasis has shown that the regulation of local and systemic cytokines plays an important role in its pathogenesis. The most often used psoriasis score is the psoriasis area and severity index (PASI). A simple laboratory test from a blood sample would be an attractive, patient-independent, and observer-independent marker of disease severity. To this end, we evaluated the association of serum levels of some proinflammatory cytokines in vivo and their correlation with severity of psoriasis. The serum levels of cytokines levels were determined with the use of the ELISA method. All mean values except IL-17 levels of patients were significantly higher than those of controls. There was a significant correlation between serum levels of IFN-gamma, IL-12, IL-17, and IL-18, and severity of the disease. Psoriasis can be described as a T-cell-mediated disease, with a complex role for a variety of cytokines, which has led to the development of new immunomodulatory therapies. In this study, serum TNF-alpha, IFN-gamma, IL-6, IL-8, IL-12, and IL-18 levels were significantly higher in active psoriatic patients than in controls. Furthermore, high levels of IFN-gamma, IL-12, and IL-18 correlated with the clinical severity and activity of psoriasis, and those measurements of serum levels of these cytokines may be objective parameters for the disease severity.     

The Role of IL-23/Th17 Pathway in Patients with Primary Immune Thrombocytopenia

Background

Primary immune thrombocytopenia (ITP) is an autoimmune bleeding disorder with an unclear etiology. This study aims to investigate the role of IL-23/Th17 pathway in patients with ITP.

Method

The gene expressions of IL-17, IL-23 and their receptors in ITP patients and healthy controls were analyzed by quantitative real-time PCR. ELISA was used to test the IL-17 and IL-23 levels in plasma. Flow cytometry was used to detect the frequency of Th17 cells. The correlation between plasma IL-23 and IL-17 levels, Th17 cells, platelets were analyzed. The level of Th17-related cytokines was measured by ELISA following stimulation with IL-23. Subsequently, the IL-23 and IL-17 levels were measured in patients post-treatment.

Results

The PBMCs of ITP patients showed increased mRNA expression levels in each of the following: IL-23p19, IL-12p40, IL-23R, IL-12Rβ1, IL-17A, IL-17F, and RORC. In addition, elevated Th17 cells and plasma IL-17, IL-23 levels were also observed in these ITP patients. Furthermore, it was found that IL-23 levels in plasma are positively correlated with IL-17 levels and Th17 cells, yet negatively correlated with platelet count. Following IL-23 stimulation in vitro, IL-17 levels showed significant elevation. Furthermore, both IL-23 and IL-17 levels decreased after effective treatment.

Conclusion

The IL-23/Th17 pathway may be involved in the pathogenesis of ITP through enhancement of the Th17 response. Moreover, our results suggest that the IL-23/Th17 pathway is a potential therapeutic target in future attempts of ITP treatment.     

Decreases in Colonic and Systemic Inflammation in Chronic HIV Infection after IL-7 Administration

Despite antiretroviral therapy (ART), some HIV-infected persons maintain lower than normal CD4⁺ T-cell counts in peripheral blood and in the gut mucosa. This incomplete immune restoration is associated with higher levels of immune activation manifested by high systemic levels of biomarkers, including sCD14 and D-dimer, that are independent predictors of morbidity and mortality in HIV infection. In this 12-week, single-arm, open-label study, we tested the efficacy of IL-7 adjunctive therapy on T-cell reconstitution in peripheral blood and gut mucosa in 23 ART suppressed HIV-infected patients with incomplete CD4⁺ T-cell recovery, using one cycle (consisting of three subcutaneous injections) of recombinant human IL-7 (r-hIL-7) at 20 µg/kg. IL-7 administration led to increases of both CD4⁺ and CD8⁺ T-cells in peripheral blood, and importantly an expansion of T-cells expressing the gut homing integrin α4β7. Participants who underwent rectosigmoid biopsies at study baseline and after treatment had T-cell increases in the gut mucosa measured by both flow cytometry and immunohistochemistry. IL-7 therapy also resulted in apparent improvement in gut barrier integrity as measured by decreased neutrophil infiltration in the rectosigmoid lamina propria 12 weeks after IL-7 administration. This was also accompanied by decreased TNF and increased FOXP3 expression in the lamina propria. Plasma levels of sCD14 and D-dimer, indicative of systemic inflammation, decreased after r-hIL-7. Increases of colonic mucosal T-cells correlated strongly with the decreased systemic levels of sCD14, the LPS coreceptor - a marker of monocyte activation. Furthermore, the proportion of inflammatory monocytes expressing CCR2 was decreased, as was the basal IL-1β production of peripheral blood monocytes. These data suggest that administration of r-hIL-7 improves the gut mucosal abnormalities of chronic HIV infection and attenuates the systemic inflammatory and coagulation abnormalities that have been linked to it.     

Serum IL-1beta, IL-2, and IL-6 in insulin-dependent diabetic children

Insulin-dependent diabetes mellitus (IDDM) is a chronic disease characterized by T-cell-dependent autoimmune destruction of the insulin-producing beta cells in the pancreatic islets of Langerhans, resulting in an absolute lack of insulin. T cells are activated in response to islet-dominant autoantigens, the result being the development of IDDM. Insulin is one of the islet autoantigens responsible for the activation of T-lymphocyte functions, inflammatory cytokine production, and development of IDDM. The aim of this study was to investigate serum concentrations of interleukin (IL)-1beta, IL-2, IL-6, and tumor necrosis factor (TNF)-alpha in children IDDM. The study population consisted of 27 children with IDDM and 25 healthy controls. Children with IDDM were divided into three subgroups: (1) previously diagnosed patients (long standing IDDM) (n : 15), (2) newly diagnosed patients with diabetic ketoacidosis (before treatment) (n : 12), and (3) newly diagnosed patients with diabetic ketoacidosis (after treatment for two weeks) (n : 12). In all stages of diabetes higher levels of IL-1beta and TNF-alpha and lower levels of IL-2 and IL-6 were detected. Our data about elevated serum IL-1beta, TNF-alpha and decreased IL-2, IL-6 levels in newly diagnosed IDDM patients in comparison with longer standing cases supports an activation of systemic inflammatory process during early phases of IDDM which may be indicative of an ongoing beta-cell destruction. Persistence of significant difference between the cases with IDDM monitored for a long time and controls in terms of IL-1beta, IL-2, IL-6, and TNF-alpha supports continuous activation during the late stages of diabetes.     

Micro RNA-19a suppresses IL-10 in peripheral B cells from patients with atherosclerosis

Background and aimsThe interleukin (IL)-10-production B cells play an important role in the pathogenesis of atherosclerosis (Asro) with unknown mechanism. Micro RNA (miR)-17-92 cluster has strong immune regulatory activities. This study tests a hypothesis that miR-17-92 cluster suppresses IL-10 expression in B cells of Asro patients.MethodsPatients with Asro were recruited into this study. Peripheral blood samples were collected from the patients. B cells were isolated from the blood samples and analyzed to elucidate the role of miR-17-92 in the regulation of IL-10 expression.ResultsPeripheral B cells from patients with Asro show lower levels of IL-10 than that from healthy subjects. The IL-10 expression in the B cells is negatively correlated with the expression of miR-19a in the B cells. The serum levels of tumor necrosis factor (TNF)-α, interferon (IFN)-γ and interleukin (IL)-4 in Asro patients were higher than healthy subjects. Exposure to TNF-α or IFN-γ or IL-4 suppressed IL-10 expression in B cells via increasing the expression of miR-19a in B cells, which could be abolished by Inhibition of miR-19a.ConclusionsTNF-α or IFN-γ or IL-4 suppresses IL-10 in B cells via up regulating miR-19a expression.     

IL-6，IL-8 的检测在鉴别良恶性胸水中的诊断价值分析

目的:分析检测血清、胸水中白细胞介素6(IL-6)、白细胞介素8(IL-8)水平对良恶性胸水的鉴别诊断价值。方法:采用酶联免疫吸附试验(ELISA)检测32例良性胸水患者和40例恶性胸水患者血清及胸水中IL-6、IL-8水平,以及30例健康体检者血清中IL-6、IL-8水平。结果:良性胸水组及恶性胸水组血清IL-6、IL-8水平均显著高于正常对照组,差异具有统计学意义(P<0.05);与恶性胸水组比较,良性胸水组胸水及血清中IL-6、IL-8水平升高更为显著(P<0.05),良性胸水组IL-6、IL-8的胸水/血清比值也显著高于恶性胸水组,差异具有统计学意义(P<0.05)。结论:胸水及血清中IL-6、IL-8的检测对良、恶性胸水患者具有鉴别诊断意义。