Soluble interleukin-6 receptor is elevated during influenza A virus infection and mediates the IL-6 and IL-32 inflammatory cytokine burst

Influenza A virus （IAV） infection is a major worldwide public health problem. However, the factors involved in mediating the inflammatory response to this infection and their relationships remain poorly understood. Here, we show that IAV infection stimulates the expression of the soluble IL-6 receptor （slL-6R）, a multifunctional protein involved in IL-6 signaling. Interestingly, slL-6R expression upregulated the levels of its own ligand, IL-6 and those of the pro-inflammatory cytokine IL-32. shRNA-mediated knockdown of slL-6R suppressed I L-6 and IL-32, indicating that this regulation is dependent on slL-6R during IAV infection. Furthermore, our results demonstrate that IL-32 participates in a negative feedback loop that inhibits slL-6R while upregulating IL-6 expression during IAV infection. Therefore, we show that slL-6R is a critical cellular factor involved in the acute inflammatory response to viral infection.

Exploring the role of interleukin-6 receptor blockade in epilepsy and associated neuropsychiatric conditions through a mendelian randomization study

BACKGROUND The interplay between inflammation,immune dysregulation,and the onset of neurological disorders,including epilepsy,has become increasingly recognized.Interleukin(IL)-6,a pro-inflammatory cytokine,is suspected to not only mediate traditional inflammatory pathways but also contribute to neuroinflammatory responses that could underpin neuropsychiatric symptoms and broader psychiatric disorders in epilepsy patients.The role of IL-6 receptor(IL6R)blockade presents an intriguing target for therapeutic intervention due to its potential to attenuate these processes.neuropsychiatric conditions due to neuroinflammation.METHODS Mendelian randomization(MR)analysis employing single nucleotide poly-morphisms(SNPs)in the vicinity of the IL6R gene(total individuals=408225)was used to evaluate the putative causal relationship between IL6R blockade and epilepsy(total cases/controls=12891/312803),focal epilepsy(cases/controls=7526/399290),and generalized epilepsy(cases/controls=1413/399287).SNP weights were determined by their effect on C-reactive protein(CRP)levels and integrated using inverse variance-weighted meta-analysis as surrogates for IL6R effects.To address potential outlier and pleiotropic influences,sensitivity analyses were conducted employing a variety of MR methods under different modeling assumptions.RESULTS The genetic simulation targeting IL6R blockade revealed a modest but significant reduction in overall epilepsy risk[inverse variance weighting:Odds ratio(OR):0.827;95%confidence interval(CI):0.685-1.000;P=0.05].Subtype analysis showed variability,with no significant effect observed in generalized,focal,or specific childhood and juvenile epilepsy forms.Beyond the primary inflammatory marker CRP,the findings also suggested potential non-inflammatory pathways mediated by IL-6 signaling contributing to the neurobiological landscape of epilepsy,hinting at possible links to neuroinflammation,psychiatric symptoms,and associated mental disorders.CONCLUSION The investigation underscored a tentative causal relationship between IL6R blockade and decreased epilepsy incidence,likely mediated via complex neuroinflammatory pathways.These results encouraged further in-depth studies involving larger cohorts and multifaceted psychiatric assessments to corroborate these findings and more thoroughly delineate the neuro-psychiatric implications of IL-6 signaling in epilepsy.The exploration of IL6R blockade could herald a novel therapeutic avenue not just for seizure management but also for addressing the broader psychiatric and cognitive disturbances often associated with epilepsy.

Serum soluble interleukin-2 receptor levels in patients with chronic hepatitis B virus infection and its relation with antiHBc

AIM： To investigate the relationship between serum soluble interleukin-2 receptor （sIL-2R） level and anti-HBc in patients with chronic hepatitis B virus （HBV） infection. METHODS： Sera from 100 patients with chronic HBV infection and 30 healthy controls were included in this study. The patients were divided into group A [HBsAg （＋）, HBeAg （＋） and anti-HBc （＋）, n = 50] and group B [HBsAg （＋）, HBeAg （＋） and anti-HBc （-）, n = 50]. sIL-2R levels were determined using ELISA. HBV DNA and alanine aminotransferase （ALT） were also detected. RESULTS： Serum sIL-2R levels were significantly higher in patients with chronic HBV infection than in healthy controls. Moreover, serum sIL-2R levels were significantly higher in patients with HBsAg （＋）, HBeAg （＋） and antiHBc （＋） （976.56±213.51×10^3 U/L） than in patients with HBsAg （＋）, HBeAg （＋） and anti-HBc （-） （393.41±189.54 ×10^3 U/L, P〈 0.01）. A significant relationship was found between serum sIL-2R and ALT levels （P〈 0.01） in patients with chronic HBV infection, but there was no correlation between sIL-2R and HBV DNA levels. The anti-HBc status was significantly related to the age of patients （P〈 0.01）. CONCLUSION： The high sIL-2R level is related to positive anti-HBc in chronic hepatitis B patients. Positive anti-HBc may be related to T-lymphocyte activation and negative anti-HBc may imply immune tolerance in these patients.

Changes in soluble interleukin-2 receptor level in serum and Na^+ -K^+ -exchanging ATPase activity in semen of infertile men caused by antisperm antibody

Aim: To explore the possible mechanisms of male infertility caused by antisperm antibody (AsAb). Methods: Thesoluble interleukin-2 receptor (sIL-2R) level in serum was analyzed by ELISA and Na^+ -K^+ -exchanging ATPase activi-ty in semen by phosphorus (Pi) assay. Results: The slL-2R level in serum was significantly higher and the Na^+ -K^+ -exchanging ATPase activity in semen significantly lower in AsAb positive infertile men when compared with thecontrols. Conclusion: The AsAb titer varies with the slL-2R level in serum. A decrease in Na^+ -K^+ -exchangingATPase activity in semen may play a role in male infertility caused by AsAb.

Study of the Effect of Leeching on Plasma Endothelin and Soluble Interleukin-2 Receptor in Patients with Systemic Lupus Erythematosus

Objective: to explore the mechanism of leeching in treating systemic lupus erythematosus (SLE). Methods: Forty-four patients with SLE were randomly divided into conventional corticosteroid treated group (control group, n =20) and conventional treatment group with leeching intervention added (leeching group, n =24). Before and after treatment the concentration of plasma endothelin (ET) and soluble interleukin-2 receptor (sIL-2R) were determined. Results: Before treatment the level of plasma ET and sIL-2R in the SLE patients were all higher than those in the normal healthy group, ( P <0.01). But after treatment the level of these in both groups were significantly improved than those of before treatment ( P <0.05), and comparison between these two treated groups showed that the difference between them was significant ( P <0.05). Conclusion: Leeching added to conventional treatment of SLE could be more effective in improving the level of plasma ET and sIL-2R, and ameliorating the impairment of renal tissues.

Elevated pancreatic enzymes, IgM, soluble interleukin-2 receptor in anti-GADab(+) type 1 diabetes

Type 1 diabetes can be classified into immune-mediated diabetes (type 1A) and idiopathic diabetes, which lacks immunological evidence for beta cell autoimmunity (type 1B). Type 1A diabetes is characterized by the presence of the anti-glutamic acid decarboxylase antibody (anti-GADab). Fulminant type 1 diabetes is classified as type 1B diabetes, and characterized by the absence of anti-GADab, flu-like symptoms, and elevated serum exocrine pancreatic enzymes. We report a type 1 diabetic patient who showed flu-like symptoms, elevated serum exocrine pancreatic enzymes, and an extremely high-titer of anti-GADab, manifesting the characteristics of both type 1A and fulminant type 1 diabetes.

Effects of Aprotinin on Serum Interleukin-2 and Soluble Interleukin-2 Receptor during Cardiopulmonary Bypass

Interleukin-2 and its receptor are of importance in regulating immunity responses. The changes of interleukin-2 (IL-2) and soluble interleukin-2 receptor (IL-2R) during heart valve (s) replacement operation and effects of aprotinin on them were observed. Twenty patients undergoing heart valve (s) replacement were randomly divided into two groups: control group (n=10) and apro- tinin group (n=10). In aprotinin group, 1 000 000 KIU aprotinin was given by vein injection and then 2 000 000 KIU was given as a bolus in prime. Blood samples were collected before CPB, right after CPB and on the 1st, 3rd and 7th postoperative day (POD) for serum IL-2 and sIL-2R determination. Results showed that after CPB, IL-2 was reduced and slL-2R increased. Meanwhile, serum IL-2R was lower in aprotinin group than that of control. It is concluded that the immunity depression after CPB is associated with low level of IL-2 and high level of sIL-2R and aprotinin can ameliorate the situation.

Glycosylation-independent binding to extracellular domains 11-13 of mannose-6-phosphate/insulin-like growth factor-2 receptor mediates the effects of soluble CREG on the phenotypic proliferation of vascular smooth muscle cells

Background The present study aimed to investigate the detailed mode and specific sites for their binding as well as the functional relevance of this binding in the phenotypic proliferation of vascular smooth muscle cells(SMCs). Methods CREG knocked-down SMCs were employed to evaluate the biological activity of wtCREG and mCREG.Expressions of SMC differentiation markers SM myosin heavy chain(SM-MHC),SM-actin,heavy caldesmon and myocardin were determined by Western blotting using specific antibodies. Cellular growth of SMCs was assessed by bromide dewuridine (BrdU) incorporation and cell cycle analysis on fluorescence-activated cell sorting(FACS).A solid-phase binding assay was used to study the binding of CREG to extracellular domains of M6P/IGF2R.The cellular co-localization of the two recombinant CREGs with M6P/IGF2R was detected on SMC surface by immunoprecipitation and immunofluorescence analysis.Results The molecular weight of wtCREG was around 30 kD while that of the mCREG was～25 kD.Treatment of wtCREG with PNGase F reduced its molecular weight from～30 kD to～25 kD,whereas PNGase F treatment had no effect on the molecular weight of mCREG.Both wtCREG and mCREG proteins enhanced SMC differentiation,inhibited BrdU incorporation,and arrested cell cycle progression when added to the culture medium.In CREG knocked-down SMCs,the amount of CREG detected by immunoblotting in M6P/IGF2R immunoprecipitates was significantly reduced when compared to normal cells.Both recombinant CREGs co-immunoprecipitated with M6P/IGF2R, although slightly reduced amount of the mutant CREG was detected in M6P/IGF2R immunoprecipitates.Immunostaining revealed that His-tagged CREGs co-localized with IGF2R on the cell surface in a glycosylation-independent manner.In vitro binding assay showed that CREGs bound to M6P/ IGF2R extracellular domains 7-10 and 11-13 in a glycosylation -dependent and -independent manner,respectively.Further blocking experiments using soluble M6P/IGF2R fragments and M6P/IGF2R neutralizing antibody indicated that the biological activities of recombinant CREGs in SMC growth and the up-regulation of SMC differentiation markers were all abolished by treatment with the M6P/IGF2R neutralizing antibody. However,although the growth inhibitory effect of wtCREG was nearly abolished by D7-10 or D11-13,the effect of mCREG was only reversed by Dll-13,indicating that the binding to domains 11-13 is required for CREG to modulate the proliferation of SMCs.Conclusions These data suggest that solubleCREG proteins can exert their biological function via binding to the extracellular domains 7-10 and 11-13 of cell surface M6P/IGF2R in both a glycosylation-dependent and -independent manner.

Plasma Levels of Growth Arrest Specific Protein (Gas6) and the Soluble Form of Its Tyrosine Kinase Receptor Axl (sAxl) in Patients with Hepatocellular Carcinoma

The aim of this study was to determine the plasma levels of vitamin K-dependent protein growth arrest-specific protein 6 (Gas6) and its soluble receptor Axl (sAxl) in patients with hepatocellular carcinoma (HCC), acute hepatitis (AH), fulminant hepatitis(FH), chronic hepatitis (CH), and liver cirrhosis (LC) and to determine whether Gas6 and sAxl can be used as biomarkers. Immunoassys were used to measure levels of plasma Gas6 and sAxl in 40 patients with HCC, 13 patients with AH, 3 patients with FH, 7 patients with LC, and 20 healthy normal adult controls (NC). Furthermore, urinary γ-carboxyglutamic acid (Gla) was measured by high performance liquid chromatography. We have addressed this issue by conducting a cross-sectional study to determine whether plasma Gas6 and sAxl levels are associated with DCP, urinary γ-Gla, and liver functions in humans. Levels of Gas6, sAxl, and γ-Gla were significantly higher in HCC as compared to those in NC, and they were significantly positive correlated. Gas6/sAxl molar ratios in HCC were significantly higher than in NC, but those ratios in AH, FH, and LC were significantly lower in NC. Furthermore, Gas6/sAxl molar ratios in HCC increased significantly in comparison with those AH and LC. The increase of Gas6, sAxl and Gas6/sAxl molar ratio were correlated with the progression and poor prognosis of HCC. Thus, Gas6 and sAxl may be useful biomarkers for HCC.

The interleukin-1 receptor antagonist (IL-1-Ra) and soluble tumor necrosis factor receptor I (sTNF RI) in periodontal disease

The course and severity of periodontitis can be significantly affected by bacterial virulence as well as host immunity dysfunction. Periodontal tissue destruction has been proved to result from cascade of cytokines synthesized by reactive cells upon stimulation by pathogenic bacteria and lipopolysaccharides within their cell membranes. The clinical use of genetically programmed cells, producing substances blocking IL-1, based on recombinant IL-1 antagonist, as well as cytokines activating fibroblasts and osteoblasts to regenerate the destroyed periodontal tissue could prove alternative to the conventional treatment. Another cytokine of interest in respect to periodontitis ethiopathogenesis is soluble tumor necrosis factor receptor I (sTNF RI). Observation of soluble TNF receptors as physiologic inhibitors of TNF led to its administration in therapeutic process as well as in therapy selected cases of aggressive periodontitis.

Tenascin C upregulates interleukin-6 expression in human cardiac myofibroblasts via toll-like receptor 4

AIM:To investigate the effect of Tenascin C(TNC)on the expression of pro-inflammatory cytokines and matrixmetalloproteinases in human cardiac myofibroblasts(CMF).METHODS:CMF were isolated and cultured from patients undergoing coronary artery bypass grafting.Cultured cells were treated with either TNC(0.1μmol/L,24 h)or a recombinant protein corresponding to different domains of the TNC protein;fibrinogen-like globe(FBG)and fibronectin typeⅢ-like repeats(TNⅢ5-7)(both 1μmol/L,24 h).The expression of the proinflammatory cytokines;interleukin(IL)-6,IL-1β,TNFαand the matrix metalloproteinases;MMPs(MMP1,2,3,9,10,MT1-MMP)was assessed using real time RT-PCR and western blot analysis.RESULTS:TNC increased both IL-6 and MMP3(P<0.01)mR NA levels in cultured human CMF but had no significant effect on the other markers studied.The increase in IL-6 mR NA expression was mirrored by an increase in protein secretion as assessed by enzymelinked immunosorbant assay(P<0.01).Treating CMF with the recombinant protein FBG increased IL-6mR NA and protein(P<0.01)whereas the recombinant protein TNⅢ5-7 had no effect.Neither FBG nor TNⅢ5-7 had any significant effect on MMP3 expression.The expression of toll-like receptor 4(TLR4)in human CMF was confirmed by real time RT-PCR,western blot and immunohistochemistry.Pre-incubation of cells with TLR4neutralising antisera attenuated the effect of both TNC and FBG on IL-6 mR NA and protein expression.CONCLUSION:TNC up-regulates IL-6 expression in human CMF,an effect mediated through the FBG domain of TNC and via the TLR4 receptor.

Soluble Interleukin 2 Receptor-Alpha (sIL-2Rα) in the Peripheral Blood of Dogs—Comparison of Malignant Neoplasia with Other Diseases

Background: Cytokines are mediators of diseases. Expression levels in the blood could be of clinical relevance. Objective: sIL-2Rα is used as a marker for different malignancies in human medicine. The aim of this study was to show if sIL-2Rα is detectable and if there is any correlation to different diseases in dogs. Methods: For this purposes sIL-2Rα concentrations in the blood were measured in healthy dogs, in dogs with different non-neoplastic diseases and benign tumors and in dogs with malignant tumors. Serum levels of sIL-2Rα were measured by using a human specific enzyme linked immunosorbent assay (ELISA). Results: Measurement of sIL-2Rα was successful in most of the samples. Dogs with diseases have significantly increased serum levels of sIL-2Rα compared to healthy controls. sIL-2Rα serum levels are higher in patients with non-neoplastic diseases and benign tumors than in those with malignant neoplasia. There is a strong correlation between sIL-2Rα and leukocyte count. Conclusion: Measurements of sIL-2Rα in serum may be helpful in detecting stages and grades of inflammation in the progression of disease. sIL-2Rα could actually not be used as an indicator for malignant diseases in dogs like in humans. The strong correlation between sIL-2Rα and the leukocyte count indicates the inflammatory response to the disease. This could be helpful in giving a prognosis in some cases, because the inflammatory reaction is of prognostic relevance in different diseases including malignant and non-malignant neoplasia. Although the results of our research studies were very promising, further studies should be performed with a canine ELISA.

DETECTION OF PLASMA SOLUBLE INTERLEUKIN－2 RECEPTOR IN PATIENTS WITH SEVERE AND CHRONIC ACTIVE HEPATITIS B

Plasma levels of soluble interleukin-2 receptor (sIL-2R) in patients with chronic active hepatitis B (CAHB) or severe hepatitis B (SHB) were measured quantitatively by 'sandwich' ELISA with monoclonal antibodies in order to explore the change of sIL-2R levels, its clinical significance,and its relation to liver damage. The results showed that the plasma sIL-2R levels in patients with CAHB and SHB were much higher than those in normal controls (P < 0. 01 ), and the level ofplasma sIL-2R in patients with SHB was greatly higher than that in patients with CAHB. These results suggest that there is close relation between plasma level of sIL-2R, the clinical types of hepatitis B,and the severity of liver damage. In addition, there is no significant difference in plasma levels of sIL-2R between acute severe hepatitis B (ASHB), subacute severe hepatitis B (SASHB), and chronic severe hepatitis B (CSHB). No relation was found between sIL-2R level and hepatitis B virusreplication activity.

血清TRAF6、activin-A、SFMC水平与子痫前期患者病情及妊娠结局的相关性

目的分析血清肿瘤坏死因子受体相关因子6(TRAF6)、糖蛋白激素-激活素A(activin-A)、可溶性纤维蛋白复合物(SFMC)水平与子痫前期患者病情及妊娠结局的相关性。方法回顾性选取2020年7月至2023年1月郑州大学第二附属医院收治的134例子痫前期患者为研究组,另选取同期健康孕检女性为对照组,根据子痫前期患者病情程度分为轻度、重度患者,所有患者均随访至分娩结束后30 d,根据本次妊娠结局是否发生不良妊娠情况将研究组分为发生、未发生患者。对比对照组和研究组、不同病情程度及不同妊娠结局患者入院时血清TRAF6、activin-A、SFMC水平,并分析其相关性,分析入院时血清各指标水平检测对子痫前期患者妊娠结局的预测价值。结果研究组入院时血清TRAF6、activin-A、SFMC水平高于对照组(P<0.05);重度患者血清TRAF6、activin-A、SFMC水平高于轻度患者(P<0.05);入院时血清TRAF6、activin-A、SFMC均与患者病情程度呈正相关(P<0.05);妊娠不良患者入院时血清TRAF6、activin-A、SFMC水平高于妊娠良好患者(P<0.05);入院时血清TRAF6、activin-A、SFMC水平联合预测子痫前期患者妊娠不良的曲线下面积(AUC)为0.748。结论血清TRAF6、activin-A、SFMC表达与子痫前期患者病情程度及预后密切相关,其三者联合检测对预测子痫前期患者妊娠不良具有较高的应用价值,可辅助临床诊疗。

Diagnostic and prognostic roles of soluble CD22 in patients with Gram-negative bacterial sepsis

BACKGROUND： Soluble CD22（sCD22） is a fragment of CD22, a B cell-specific membrane protein that negatively regulates B-cell receptor signaling. To date, sCD22 has only been regarded as a tumor marker of B-cell malignancies. Its expression in infectious diseases has not yet been assessed.METHODS： Serum concentrations of sCD22, procalcitonin（PCT） and interleukin-6（IL-6） were measured by enzymelinked immunosorbent assays in patients with intra-abdominal Gram-negative bacterial infection. Receiver operating characteristic curve analysis was performed to evaluate the diagnostic accuracy of these biomarkers in this type of infection. The correlations between biomarkers and the Acute Physiology and Chronic Health Evaluation（APACHE） II scores were also analyzed.RESULTS： Concentrations of sCD22 were significantly elevated in patients with sepsis and the elevation is correlated with the severity of sepsis. sCD22 was also slightly elevated in patients with non-infected systemic inflammatory response syndrome or local infection. The diagnostic accuracy of sCD22 for sepsis was equivalent to that of PCT or IL-6. In addition, the correlation of sCD22 with APACHE II scores was stronger than that of PCT or IL-6.CONCLUSIONS： Serum sCD22 is a novel inflammatory mediator released during infection. This soluble biomarker plays a potential role in the diagnosis of Gram-negative bacterial sepsis, with a diagnostic accuracy as efficient as that of PCT or IL-6. Furthermore, sCD22 is more valuable to predict the outcomes in patients with sepsis than PCT or IL-6. The present study suggested that sCD22 might be potentially useful in supplementing current criteria for sepsis.

Monocyte chemotactic protein-1 and soluble adhesion molecules as possible prognostic markers of the efficacy of antiviral treatment in chronic hepatitis C

AIM:To explain the role of Monocyte chemotactic protein-1 (MCP-1) and soluble adhesion molecules in chronic hepatitis C during the treatment of interferon alpha (IFNα) 2 b and ribavirin (RBV). METHODS:Concentrations of MCP-1,soluble adhesion molecules intercellular adhesion molecule-1 (sICAM-1),sP- selectin,interleukin (IL) 6,and IL10 in serum were estimated in the group of 40 patients with chronic hepatitis C treated with IFNalpha2 b and RBV in 0,16,32,48 wk of the therapy, RESULTS:In chronic hepatitis C,before and during the treatment,the serum levels of MCP-1 and sP-selectin in responders were similar to those of healthy subjects.In non- responders (NR),MCP-1 increased in the course of IFNc^+RBV treatment,differences were statistically significant as compared to responders.MCP-1 correlated statistically with the activity of periportal inflammation (r=0.35,P<0.05) but not with staging of liver fibrosis,sICAM-1 positively correlated with inflammatory activity and fibrosis in NR.sP-selectin did not correlate with histological findings in the liver.The MCP-1 correlated with the soluble form of sP-selectin concentrations (r= 6,P<0.001) and with IL-10 level in NR (r=0.4,P<0.05).There was no correlation observed between the concentration of MCP-1 and sICAM-1,IL-6 during the treatment. CONCLUSION:MCP-1 concentration may be a prognostic marker of the efficacy of IFN+RBV therapy in patients with chronic hepatitis C.

Severe acute respiratory syndrome coronavirus 2 infection: Role of interleukin-6 and the inflammatory cascade

Since December 2019,a novel coronavirus that represents a serious threat to human lives has emerged.There is still no definite treatment for severe cases of the disease caused by this virus,named coronavirus disease 2019(COVID-19).One of the most considered treatment strategies targets the exaggerated immune regulator,and interleukin(IL)-6 is a crucial pro-inflammatory mediator.Severe acute respiratory syndrome coronavirus 2(SARSCoV-2)cases show an elevated level of IL-6 related to disease severity.IL-6 activity can be inhibited by the following:IL-6 itself,IL-6 signaling pathways such as Janus kinase and signal transducer and activator of transcription(JAK-STAT),gp130,IL-6R,and downstream activated ILs,such as IL-17 and IL-6 cytokine.Currently,according to these studies and their results,IL-6 blockade with anti-IL-6 or its receptor antibodies such as tocilizumab in COVID-19 is beneficial in severe cases and may reduce the mortality rate.JAK-STAT inhibitors block the cytokine storm by inhibiting several crucial pro-inflammatory mediators such as TNF-αand IL-6 and have shown various results in clinical trials.IL-6 induces IL-17 secretion,and IL-17 is involved in the pathogenesis of inflammatory processes.Clinical trials of anti-IL-17 drugs are currently recruiting,and anti-gp130 antibody is preclinical.However,this agent has shown positive effects in inflammatory bowel disease clinical trials and could be tested for SARS-CoV-2.This study aimed to review the role of IL-6 in the cytokine storm and studies regarding IL-6 and blockade of its inflammatory pathways in COVID-19 to determine if any of these agents are beneficial for COVID-19 patients.

Effect of remifentanil on toll-like receptor 4, NF-κB and IL-6 in rabbit myocardial ischemia/reperfusion model

Objective： To investigate whether remifentanil induced cardioprotecting effect is associated with expression of toll-like receptor 4 （TLR4）, nuclear factor rB （NF-r.B） and serum interleukin -6 （IL-6）. Methods： Fifty rabbits were randomly divided into 5 groups （n=10） according to the treatment： sham operation group （group A）, ischemla-reperfusion group （group B）, low-dose remifentanil group （group C）, mediate-dose remifentanil group （group D）, and high-dose remlfentanil group （group E） Myocardial TLR4 mRNA levels, NF-r.B protein expression and serum levels of IL-6 were observed in 120 min after reperfusion. Results： The myocardial expressions of TLR4 mRNA, NF-rd3 protein and IL-6 level in sera of groups B, C, D and E were elevated compared with group A. However, remifentanil significantly reduced the levels of TLR4 mRNA, NF- r.B protein expression and serum IL-6 in groups C, D and E compared with group B. There were remarkable differences between the groups （P〈O.O1）. Conclusion： Intravenous remifentanil has protective effect against rabbit myocardial ischemia/reperfusion injury. This effect may be associated with TLR4, NF-r.B expressions on myocytes and serum level of IL-6 in a dose-dependent manner

Chemokine receptor 8 expression may be linked to disease severity and elevated interleukin 6 secretion in acute pancreatitis

BACKGROUND Acute pancreatitis(AP)is an inflammatory disease,which presents with epigastric pain and is clinically diagnosed by amylase and lipase three times the upper limit of normal.The 2012 Atlanta classification stratifies the severity of AP as one of three risk categories namely,mild AP(MAP),moderately severe AP(MSAP),and severe AP(SAP).Challenges in stratifying AP upon diagnosis suggest that a better understanding of the underlying complex pathophysiology may be beneficial.AIM To identify the role of the chemokine receptor 8(CCR8),expressed by T-helper type-2 Lymphocytes and peritoneal macrophages,and its possible association to Interleukin(IL)-6 and AP stratification.METHODS This study was a prospective case-control study.A total of 40 patients were recruited from the Chris Hani Baragwanath Academic Hospital and the Charlotte Maxeke Johannesburg Academic Hospital.Bioassays were performed on 29 patients(14 MAP,11 MSAP,and 4 SAP)and 6 healthy controls as part of a preliminary study.A total of 12 mL of blood samples were collected at Day(D)1,3,5,and 7 post epigastric pain.Using multiplex immunoassay panels,real-time polymerase chain reaction(qRT-PCR)arrays,and multicolour flow cytometry analysis,immune response-related proteins,genes,and cells were profiled respectively.GraphPad Prism^(TM) software and fold change(FC)analysis was used to determine differences between the groups.P<0.05 was considered significant.RESULTS The concentration of IL-6 was significantly different at D3 post epigastric pain in both the MAP group and MSAP group with P=0.001 and P=0.013 respectively,in a multiplex assay.When a FC of 2 was applied to identify differentially expressed genes using RT2 Profiler,CCR8 was shown to increase steadily with disease severity from MAP(1.33),MSAP(38.28)to SAP(1172.45)median FC.Further verification studies using RT-PCR showed fold change increases of CCR8 in MSAP and SAP ranging from 1000 to 1000000 times when represented as Log10,compared to healthy control respectively at D3.The findings also showed differing lymphocyte and monocyte cell frequency between the groups.With monocyte population frequency as high as 70%in MSAP at D3.CONCLUSION The higher levels of CCR8 and IL-6 in the severe patients and immune cell differences compared to MAP and controls provide an avenue for exploring AP stratification to improve management.

高尿酸痛风患者血清sICAM-1、IL-6、sCD163水平的变化及临床意义

目的检测高尿酸痛风患者血清可溶性细胞间黏附分子-1(sICAM-1)、白细胞介素-6(IL-6)、可溶性单核巨噬细胞血红蛋白清道夫受体(sCD163)水平并探讨其临床意义。方法选取2020年1月至2023年1月南阳豫西健和医院收治的200例高尿酸血症(HUA)患者纳入研究,其中92例痛风患者作为观察组,108例无症状患者作为对照组,所有患者均检测血清sICAM-1、IL-6、sCD163水平及血尿酸含量。比较两组患者的血清sICAM-1、IL-6、sCD163水平及血尿酸含量。采用Pearson相关性、多元线性回归分析血清sICAM-1、IL-6、sCD163水平与血尿酸含量的相关性。采用相对危险度(RR)分析血清sICAM-1、IL-6、sCD16对高尿酸痛风发病风险的影响,绘制受试者工作特征曲线(ROC)评价血清sICAM-1、IL-6、sCD163对高尿酸痛风的诊断价值。结果观察组患者的血清sICAM-1、IL-6、sCD163水平和血尿酸含量分别为(574.26±95.22)ng/mL、(50.12±8.27)ng/L、(825.83±198.22)pg/mL、(582.37±156.92)μmol/L,明显高于对照组的(401.47±42.83)ng/mL、(39.82±6.13)ng/L、(694.28±114.83)pg/mL、(425.77±114.83)μmol/L,差异均有统计学意义(P<0.05);经Pearson相关性分析结果显示,高尿酸痛风患者血清sICAM-1、IL-6、sCD163水平与血尿酸水平呈显著正相关(P<0.05);经线性回归建立回归模型分析结果显示,高尿酸痛风患者血清sICAM-1、IL-6、sCD163水平与血尿酸水平呈极显著相关(P<0.01);HUA患者血清sICAM-1≥483.41 ng/mL、IL-6≥44.70 ng/L、sCD16≥598.93 pg/mL时,高尿酸痛风发病风险分别是血清sICAM-1<483.41 ng/mL、IL-6<44.70 ng/L、sCD16<598.93 pg/mL的5.133倍(95%CI:3.181~8.285)、4.412倍(95%CI:2.820~6.903)、3.600倍(95%CI:2.388~5.428);经ROC分析结果显示,血清sICAM-1、IL-6、sCD163诊断高尿酸痛风的曲线下面积(AUC)分别为0.775、0.731、0.792,进一步分析结果显示,血清sICAM-1、IL-6、sCD163联合诊断AUC为0.940,明显较各时间点单个指标大(P<0.05)。结论高尿酸痛风患者血清sICAM-1、IL-6、sCD163明显升高,且与血尿酸密切相关,临床检测其水平有助于疾病诊断。