Low interleukin-10 level indicates a good prognosis in Salmonella enterica serovar typhimurium-induced pediatric hemophagocytic lymphohistiocytosis:A case report

BACKGROUND Secondary hemophagocytic lymphohistiocytosis(sHLH)triggered by Salmonella enterica serovar Typhimurium is rare in pediatric patients.There is no consensus on how to treat S.typhimurium-triggered sHLH.CASE SUMMARY A 9-year-old boy with intermittent fever for 3 d presented to our hospital with positive results for S.typhimurium,human rhinovirus,and Mycoplasma pneumoniae infections.At the time of admission to our institution,the patient’s T helper 1/T helper 2 cytokine levels were 326 pg/mL for interleukin 6(IL-6),9.1 pg/mL for IL-10,and 246.7 pg/mL for interferon-gamma(IFN-γ),for which the ratio of IL-10 to IFN-γwas 0.04.In this study,the patient received meropenem,linezolid,and cefoperazone/sulbactam in combination with high-dose methylprednisolone therapy(10 mg/kg/d for 3 d)and antishock supportive treatment twice.After careful evaluation,this patient did not receive HLH chemotherapy and recovered well.CONCLUSION S.Typhimurium infection-triggered sHLH patient had a ratio of IL-10 to IFN-γ≤1.33,an IL-10 concentration≤10.0 pg/mL,and/or an IFN-γconcentration≤225 pg/mL at admission.Early antimicrobial and supportive treatment was sufficient,and the HLH-94/2004 protocol was not necessary under these conditions.

Effect of T-regulatory cells and interleukin-35, interleukin-10, and transforming growth factor-beta on diffuse large B-cell lymphoma

BACKGROUND Diffuse large B-cell lymphoma(DLBCL)is an aggressive non-Hodgkin lymphoma that affects B lymphocytes.It can develop in the lymph nodes and can be localized or generalized.Despite DLBCL being considered potentially curable,little research has been conducted on the relationship between the body's immune response and DLBCL.AIM To study the expression and significance of T-regulatory cells(Tregs)interleukin(IL)-35,IL-10,and transforming growth factor-beta(TGF-β)in DLBCL.METHODS Data from 82 patients with DLBCL who were initially admitted to The First Affiliated Hospital of Ningbo University(Zhejiang Province,China)between January 2017 and June 2022 and treated with standard first-line regimens were reviewed.Three patients were lost to follow-up;thus,79 patients were included in the statistical analysis and then divided into three groups according to the evaluation of clinical efficacy:Incipient(new-onset and treatment-naïve),effectively treated,and relapsed-refractory.Thirty healthy individuals were included in the control group.The expression of peripheral blood T lymphocytes and their associated factors IL-35,IL-10,and TGF-βin the four groups were observed.RESULTS In contrast to the successfully treated and normal control groups,both the incipient and relapse-refractory groups exhibited greater proportions of CD4-positive(+)Tregs(P<0.05),whereas the proportion of CD8+Tregs did not differ substantially between the groups.Serum levels of IL-35 and IL-10 in the incipient and relapsed-refractory groups were higher than those in the effectively treated and normal control groups(P<0.05).There was no statistically significant distinction in the expression level of TGF-βbetween the groups(P>0.05).The correlation between IL-35 and IL-10 concentrations was significantly positive,with a correlation coefficient of 0.531(P<0.05).The correlation between IL-35 and TGF-βconcentration was significantly positive,with a correlation coefficient of 0.375(P<0.05).The correlation between IL-10 and TGF-βconcentration was significantly positive,with a correlation coefficient of 0.185(P<0.05).The expression concentrations of IL-35,IL-10 and TGF-βwere apparently and positively correlated(P<0.05).CONCLUSION Tregs IL-35,and IL-10 may be closely associated with the occurrence and development of DLBCL and the detection of related indices may be helpful in the analysis of disease prognosis.

慢加急性乙型肝炎肝衰竭患者外周血单个核细胞IP-10和COX-2水平变化及其临床意义探讨

目的 探讨乙型肝炎病毒相关慢加急性肝衰竭(HBV-ACLF)患者外周血单个核细胞(PBMC)干扰素诱导蛋白-10(IP-10)和环氧化酶-2(COX-2)水平变化及其临床意义。方法 2019年1月~2021年3月我院收治的73例HBV-ACLF患者和95例慢性乙型肝炎(CHB)患者,分离PBMCs,采用RT-PCR法检测PBMC IP-10和COX-2mRNA水平,采用化学发光法检测血清HBsAg水平,采用ELISA法检测血清IFN-γ水平。结果 HBV-ACLF组血清IFN-γ及PBMC IP-10 mRNA和COX-2 mRNA水平分别为(59.3±7.9)ng/L、(0.9±0.1)和(1.6±0.2),显著高于CHB组【分别为(35.8±6.2)ng/L、(0.6±0.1)和(0.5±0.1),P<0.05】;HBV-ACLF患者PBMC IP-10和COX-2水平与血清HBsAg水平呈负相关(r=-0.828,P<0.05;r=-0.795,P<0.05);29例死亡组血清IFN-γ及PBMC IP-10 mRNA和COX-2 mRNA水平分别为(67.5±8.1)ng/L、(1.2±0.2)和(1.9±0.4),显著高于44例生存组【分别为(53.9±7.4)ng/L、(0.7±0.1)和(1.4±0.2),P<0.05】;应用PBMC IP-10和COX-2水平评估HBV-ACLF患者预后的AUC分别为0.835和0.828,两者差异无统计学意义(P>0.05);32例PBMC IP-10 mRNA≥0.9患者90 d生存率为46.9%,显著低于41例IP-10 mRNA<0.9患者的70.7%(P<0.05),38例COX-2 mRNA≥1.7患者90 d生存率为47.4%,显著低于35例COX-2 mRNA<1.7患者的74.3%(P<0.05)。结论 检测HBV-ACLF患者PBMC IP-10和COX-2水平可能能帮助预测其短期预后,值得进一步研究。

Relationship between the expression of IP-10 and IP-10 mRNA in peripheral blood and HBV DNA level in patients with cirrhosis

BACKGROUND: Post-hepatitic cirrhosis is regarded as common and severe form of liver damage. Interferon gamma-inducible protein 10 (IP-10), a member of the non-ELR (glutamic-leucine-arginine) motif CXC chemokine family, has recently been shown to recruit and activate specific subsets of leukocytes to sites of inflammation or an immune response during the development of hepatic cirrhosis. However, the effects of IP-10 and IP-10 mRNA on inflammatory infiltration at local sites and in the peripheral blood of patients with post-hepatitic cirrhosis as well as their relationship with viral load are still poorly defined. This study aimed to detect the relationship between the expression of IP-10 in serum, IP-10 mRNA in peripheral blood mononuclear cells (PBMCs), and the levels of HBV DNA in the serum of patients, and to explore their role in the pathogenesis of cirrhosis. METHODS: Typical patients with cirrhosis after HBV infection were selected, and their serum IP-10 concentrations were evaluated with ELISA, the content of IP-10 mRNA in PBMCs was measured by real-time PCR, and the load of HBV DNA in serum and PBMCs was assessed by semi-quantitative analysis of gel imaging. RESULTS: The levels of IP-10 in serum and IP-10 mRNA in PBMCs of patients with cirrhosis were 299.9 +/- 77.2 pg/ml and 0.7500 +/- 0.1495, respectively. They were higher than those of controls (P<0.05) and also increased in the HBV DNA(+) groups (P<0.05, P<0.01) to 343.0 +/- 80.3 pg/ml and 0.8465 +/- 0.1528, respectively. The levels of IP-10 in serum and IP-10 mRNA in PBMCs were clearly correlated with the load of HBV DNA (P<0.01). CONCLUSIONS: The levels of IP-10 and IP-10 mRNA in the peripheral blood of patients with cirrhosis increase are closely correlated with the load of HBV DNA in serum, and play a key role in the progression of post-hepatitic cirrhosis. (Hepatobiliary Pancreat Dis Int 2010; 9: 280-286)

Why interleukin-10 supplementation does not work in Crohn's disease patients

Inflammatory bowel diseases (IBD) such as Crohn's disease (CD) or ulcerative colitis are chronic intestina disorders, which are on the increase in "Westernised" countries. IBD can be caused by both genetic and environmental factors. Interleukin-10 (IL-10) is an immunoregulatory cytokine that has been identified as being involved in several diseases including IBD. Studies have shown that polymorphisms in the promoter region reduce serum levels of IL-10 and this reduction has been associated with some forms of IBD. Mouse models have shown promising results with IL-10 supplementation, as such IL-10 supplementation has been touted as being a possible alternative treatment for CD in humans. Clinical trials have shown that recombinant human IL-10 is safe and well tolerated up to a dose o 8 μg/kg. However, to date, the results of the clinica trials have been disappointing. Although CD activity was reduced as measured by the CD activity index IL-10 supplementation did not result in significantly reduced remission rates or clinical improvements when compared to placebo. This review discusses why IL-10supplementation is not effective in CD patients currently and what can be addressed to potentially make IL-10 supplementation a more viable treatment option in the future. Based on the current research we conclude that IL-10 supplementation is not a one size fits all treatment and if the correct population of patients is chosen then IL-10 supplementation could be of benefit.

Interleukin-6 and ratio of plasma interleukin-6/interleukin-10 as risk factors of symptomatic lumbar osteoarthritis

AIM To determine the role of cartilage oligomeric matrix protein(COMP), interleukin(IL)-6, IL-10 and ratio of IL-6/IL-10 as risk factors of symptomatic lumbar osteoarthritis(OA) in postmenopausal women with estrogen deficiency.METHODS Case-control study had been conducted in Sanglah General Hospital from October 2015 until March 2016. The blood samples were obtained and analyzed by enzyme-linked immunosorbent assay(ELISA).RESULTS From 44 pairs of samples which divided into 44 samples as case group and 44 samples as control group showed that high level of COMP in estrogen deficiency postmenopausal women were not at risk(OR = 0.7; 95%CI: 0.261-1.751; P = 0.393) for symptomatic lumbar OA(cut-off point 0.946). Estrogen deficiency in postmenopausal women with the high level of IL-6 had 2.7 times risk(OR = 2.7; 95%CI: 0.991-8.320; P = 0.033) for symptomatic lumbar OA from the low level of IL-6(cut-off point 2.264). At lower level of IL-10, there was no risk for symptomatic lumbar OA(OR = 0.6; 95%CI: 0.209-1.798; P = 0.345) than with the higher level of IL-10(cut-off point 6.049). While the high ratio of IL-6/IL-10 level in estrogen deficiency postmenopausal women gave 3.4 times risk(OR = 3.4; 95%CI: 1.204-11.787; P = 0.011)for symptomatic lumbar OA than the low ratio of IL-6/IL-10 level(cut-off point 0.364).CONCLUSION High ratio of IL-6/IL-10 plasma level was the highest risk factor for causing symptomatic lumbar OA in postmenopausal women with estrogen deficiency.

Association of interleukin-10 polymorphisms with risk of irritable bowel syndrome:A meta-analysis

AIM:To clarify the current understanding of the association between interleukin-10(IL-10)polymorphisms and the risk of irritable bowel syndrome(IBS).METHODS:We searched for studies in any language recorded in PubMed,Embase and Cochrane library before August 2013.The associations under allele contrast model,codominant model,dominant model,and recessive model were analyzed.The strengths of the association between IL-10 polymorphisms and IBS risk were estimated using odds ratios(OR)with 95%confidence interval(CI).Fixed effects model was used to pool the result if the test of heterogeneity was not significant,otherwise the random-effect model was selected.RESULTS:Eight case-control studies analyzing three single-nucleotide polymorphisms rs1800870(-1082 A/G),rs1800871(-819C/T),and rs1800872(-592A/C)of the IL-10 gene,which involved 928 cases and 1363 controls,were eligible for our analysis.The results showed that rs1800870 polymorphisms were associated with a decreased risk of IBS(GG+GA vs AA:OR=0.80,95%CI:0.66-0.96),(AA+GA vs GG:OR=0.68,95%CI:0.52-0.90).Subgroup analysis revealed such association only existed in Caucasian ethnicity(AA+GA vs GG,OR=0.70,95%CI:0.55-0.89).The rs1800872 polymorphisms were associated with an increased risk of IBS in Asian ethnicity(CC vs GG:OR=1.29,95%CI:1.01-1.16).There were no associations between rs1800871 polymorphisms and the IBS risk.CONCLUSION:The results suggest that IL-10 rs1800870confers susceptibility to the risk of IBS in Caucasian ethnicity,and the rs1800872 may associate with IBS risk in Asians.However,no significant associations are found between rs1800871 and IBS risk.

Restraint stress induces and exacerbates intestinal inflammation in interleukin-10 deficient mice

AIM:To investigate the effects of restraint stress on chronic colitis in interleukin(IL)-10 deficient(IL-10^(-/-))mice.METHODS:The first experiment compared the effect of restraint stress on the development of intestinal inflammation in wild-type and IL-10^(-/-) mice.Both wildtype and IL-10^(-/-) mice were physically restrained in a well-ventilated,50 cm3 conical polypropylene tube for2 h per day for three consecutive days.The second experiment was performed to assess the effect of restraint stress on exacerbation of colitis induced by piroxicam in IL-10^(-/-) mice.The IL-10^(-/-) mice were exposed to restraint stress for 2 h per day for 3consecutive days,and then treated with piroxicam for4 d at a dose of 200 ppm administered in the rodent chow.RESULTS:In the first experiment,none of the wildtype mice with or without restraint stress showed clinical and histopathological abnormality in the gut.However,IL-10^(-/-) mice exposed to restraint stress exhibited histologically significant intestinal inflammation as compared to those without restraint stress.In the second experiment,restraint stress significantly reduced body weight and increased the severity of intestinal inflammation assessed by histopathologic grading in IL-10^(-/-) mice.Colonic IL12p40 mRNA expression was strongly increased in mice exposed to restraint stress.CONCLUSION:This novel animal model could be useful in future study of psychological stress in the pathogenesis of inflammatory bowel disease.

Metabolic syndrome attenuates ulcerative colitis: Correlation with interleukin-10 and galectin-3 expression

BACKGROUND Ulcerative colitis(UC)is a chronic disease characterized by inflammation of intestinal epithelium,primarily of the colon.An increasing prevalence of metabolic syndrome(MetS)in patients with UC has been documented recently.Still,there is no evidence that MetS alters the course of the UC.AIM To test the influence of the MetS on the severity of UC and the local and systemic immune status.METHODS Eighty nine patients with de novo histologically confirmed UC were divided in two groups,according to ATP III criteria:Group without MetS(no MetS)and group with MetS.RESULTS Clinically and histologically milder disease with higher serum level of immunosuppressive cytokine interleukin-10(IL-10)and fecal content of Galectin-3(Gal-3)was observed in subjects with UC and MetS,compared to subjects suffering from UC only.This was accompanied with predomination of IL-10 over pro-inflammatory cytokines tumor necrosis factorα(TNF-α),interleukin-6(IL-6),and interleukin-17(IL-17)in the sera as well as Gal-3 over TNF-αand IL-17 in feces of UC patients with MetS.Further,the patients with both conditions(UC and MetS)had higher percentage of IL-10 producing and Gal-3 expressing innate and acquired immune cells in lamina propria.CONCLUSION Local dominance of Gal-3 and IL-10 over pro-inflammatory mediators in patients with MetS may present a mechanism for limiting the inflammatory process and subsequent tissue damage in UC.

Research advances of vasoactive intestinal peptide in the pathogenesis of ulcerative colitis by regulating interleukin-10 expression in regulatory B cells

Ulcerative colitis(UC)is a chronic relapsed intestinal disease with an increasing incidence around the world.The pathophysiology of UC remains unclear.However,the role of the interaction between the enteric nervous system and the immune system in the pathogenesis of UC has been the focus of attention and has become a research hotspot.Vasoactive intestinal peptide(VIP)is a kind of endogenous neuropeptide with regulatory activity on intestinal immunity.It has been shown to regulate immune disorders in animal and human experiments and has become an effective anti-inflammatory and immune modulator that affects the innate immune system and adaptive immune system.Regulatory B cells(Bregs)are a new group of B cells that negatively regulate the immunity and have received extensive attention in immune circles.Bregs can regulate immune tolerance by producing interleukin(IL)-10,IL-35,and transforming growth factor-β,suppressing autoimmune diseases or excessive inflammatory responses.The secretion of IL-10 by Bregs induces the development of T helper(Th)0 and Th2 cells.It also induces Th2 cytokines and inhibits Th1 cytokines,thereby inhibiting Th1 cells and the Th1/Th2 balance.With further clarity on the mechanism of the regulation of IL-10 expression by VIP in Bregs in colitis patients,we believe that Bregs can provide a novel strategy for the clinical treatment of UC.Thus,we aim to review the current literature on this evolving topic.

Interleukin-10 promoter polymorphisms in patients with hepatitis B virus infection or hepatocellular carcinoma in Chinese Han ethnic population

BACKGROUND: Since single nucleotide polymorphisms (SNPs) can serve as gene markers, polymorphism profiles may help scientists to identify the full collection of genes that contribute to the development of complex diseases such as cancer. The distribution of interleukin-10 (IL-10) promoter polymorphisms in Chinese Han ethnic patients with hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC) was investigated in this study. METHODS: The polymorphisms of IL-10 promoter region were detected by pulymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and sequencing. Sixty-six health controls, 42 patients with HBV infection, 30 HCC patients, and cell line SMMC-7721 were examined this way. RESULTS: Polyrnorphisms of T/C or T/N on-872 site occurred frequently in Han ethnic population. Pulyrnorphisms were detected in HBV and HCC patients and cell line SMMC-7721. The hotspot among the pulymorphisms was inserting base A between-1058 and-1057. CONCLUSION: Polymorphisms of IL-10 promoter in HBV and HCC patients may be associated with HBV infection and HCC development.

Increased vitreal levels of interleukin-10 in diabetic retinopathy:a Meta-analysis

AIM:To conduct a Meta-analysis for the change of interleukin-10(I1-10)concentration in vitreous samples of patients with diabetic retinopathy(DR).METHODS:Systemic search for literature was conducted from the databases of PubMed,Web of Science and Cochrane Library by August 2019.Statistical analyses including standard mean difference(SMD)and its 95%confidence interval(CI)were performed by using RevMan 5.3 software.RESULTS:Totally 194 studies were screened and finally 11 studies were included in the Meta-ana lysis.The concentration of IL-10 in the DR group was higher than in the control group(P=0.003.SMD:0.77.95%CI:0.25-1.28).Significant heterogeneity was found among all studies(P<0.00001,I^2=92%).The subgroup analysis showed that the concentration of IL-10 increased in vitreous samples from patients with DR compared to the non-DR controls(P=0.004.SMD:1.44.95%CI:0.46-2.42).Moreover,the concentration of IL-10 in samples of proliferative diabetic retinopathy(PDR)patients was significantly higher than that of non-proliferative diabetic retinopathy(NPDR)patients(P=0.01.SMD:0.61.95%CI:0.13-1.08).CONCLUSION:The vitreal concentration of IL-10 is significantly increased in patients with DR.Further studies are needed to reveal the mechanisms of IL-10 in DR.

Mast cell deficiency exacerbates inflammatory bowel symptoms in interleukin-10-deficient mice

AIM: To test the role of mast cells in gut inflammation and colitis using interleukin(IL)-10-deficient mice as an experimental model.METHODS: Mast cell-deficient(KitW-sh/W-sh) mice were crossbred with IL-10-deficient mice to obtain double knockout(DKO) mice. The growth, mucosal damage and colitis status of DKO mice were compared with their IL-10-deficient littermates.RESULTS: DKO mice exhibited exacerbated colitis compared with their IL-10-deficient littermates, as shown by increased pathological score, higher myeloperoxidase content, enhanced Th1 type pro-inflammatory cytokines and inflammatory signaling, elevated oxidative stress, as well as pronounced goblet cell loss. In addition, deficiency in mast cells resulted in enhanced mucosal damage, increased gut permeability, and impaired epithelial tight junctions. Mast cell deficiency was also linked to systemic inflammation, as demonstrated by higher serum levels of tumor necrosis factor α and interferon γ in DKO mice than that in IL-10-deficient mice.CONCLUSION: Mast cell deficiency in IL-10-deficient mice resulted in systematic and gut inflammation, impaired gut barrier function, and severer Th1-mediated colitis when compared to mice with only IL-10-deficiency. Inflammation and impaired gut epithelial barrier function likely form a vicious cycle to worsen colitis in the DKO mice.

Genetic association and epistatic interaction of the interleukin-10 signaling pathway in pediatric inflammatory bowel disease

AIM To study the genetic association and epistatic interaction of the interleukin(IL)-10 and IL-10/STAT3 pathways in pediatric inflammatory bowel disease(IBD). METHODS A total of 159 pediatric inflammatory IBD patients(Crohn's disease,n = 136; ulcerative colitis,n = 23) and 129 matched controls were studied for genetic association of selected single nucleotide polymorphisms(SNPs) of the IL-10 gene and the genes IL10 RA,IL10 RB,STAT3,and HO1,from the IL-10/STAT3 signaling pathway. As interactions between SNPs from different loci may significantly affect the associated risk for disease,additive(a) and dominant(d) modeling of SNP interactions was also performed to examine highorder epistasis between combinations of the individual SNPs. RESULTS The results showed that IL-10 rs304496 was associated with pediatric IBD(P = 0.022),but no association was found for two other IL-10 SNPs,rs1800872 and rs2034498,or for SNPs in genes IL10 RA,IL10 RB,STAT3,and HO1. However,analysis of epistatic interaction among these genes showed significant interactions:(1) between two IL-10 SNPs rs1800872 and rs3024496(additive-additive P = 0.00015,Bonferroni P value(Bp) = 0.003);(2) between IL-10 RB rs2834167 and HO1 rs2071746(dominant-additive,P = 0.0018,Bp = 0.039); and(3) among IL-10 rs1800872,IL10 RB rs2834167,and HO1 rs2071746(additivedominant-additive,P = 0.00015,Bp = 0.005),as well as weak interactions among IL-10 rs1800872,IL-10 rs3024496,and IL-10RA(additive-additive-additive,P = 0.003; Bp = 0.099),and among IL10 RA,IL10 RB,and HO1 genes(additive-dominant-additive,P = 0.008,Bp = 0.287).CONCLUSION These results indicate that both the IL-10 gene itself,and through epistatic interaction with genes within the IL-10/STAT3 signaling pathway,contribute to the risk of pediatric IBD.

Regulation of lipoxygenase-1 and Dectin-1 on interleukin-10 in mouse Aspergillus fumigatus keratitis

AIM： To investigate the regulation of lipoxygenase （LOX）-1 and Dectin-1 on interleukin-10 （IL-10） production in mice with Aspergillus fumigatus （A. fumigatus） keratitis. METHODS： The corneas of C57BL/6 mice were pretreated with LOX-1 inhibitor Poly（I） or Dectin-1 siRNA separately before the infection of A. fumigatus. Polymerase chain reaction （PCR） and Western blot were used to detect the expression of IL-10. RESULTS： The mRNA and protein expressions of IL-10 were significantly increased in mice with A. fumigatus keratitis. Compared with the group pretreated with sterile water before infection, Poly（I） pretreatment suppressed IL-10 expression significantly. Compared with the group pretreated with scrambled siRNA before infection, Dectin-1 siRNA pretreatment significantly reduced IL-10 expression in response to A. fumigatus infection. CONCLUSION： LOX-1 and Dectin-1 regulate IL-10 production in mouse A. fumigatus keratitis.

CD14 macrophage and IL-10 levels in the peripheral blood of breast cancer patients and their diagnostic value

Objective To explore the correlation between macrophages and interleukin-10(IL-10 in the peripheral blood of breast cancer(BC)patients and the diagnostic value of joint detection.Methods BC patients(n=50)and healthy controls(n=40)were prospectively recruited.The percentage of circulating cluster of differentiation 14(CD 14)macrophage cells was analyzed by flow cytometry,and an enzyme-linked immunosorbent assay(ELISA)was used to detect IL-10 expression levels.Receiver operating characteristic(ROC)curves were used to verify the diagnostic value of the models based on the expression of CD14 macrophage cell populations and IL-10.In addition,the association between model expression and clinicopathological characteristics was investigated.Another 30 patients with BC and 30 with benign breast disease were selected to validate the IL-10 and CD14 macrophage joint detection model using the same method.Results CD14 macrophage and IL-10 expression levels in BC patients were higher than those in healthy controls(P<0.05).The ROC curve showed that the area under the curve(AUC)of CD14+macrophages combined with IL-10 was 0.830,the sensitivity was 72.0%,and the specificity was 87.5%.Its diagnostic efficiency was better than all other single and joint detections.Correlation analysis of clinicopathological features showed that IL-10 and CD14+macrophage joint detection was significantly correlated with tumor size,tumor-node-metastasis(TNM)stage,and lymph node,estrogen receptor(ER),and Ki-67 expression(P<0.05).The validation analysis results were consistent with the test results.Conclusion Peripheral blood macrophages can be an independent diagnostic marker for BC.Joint detection of CD14-macrophages and IL-10 suggests poor prognosis,which has unlimited potential to guide BC development and provides a new theory for studying tumor-associated macrophages in BC.

超声血流参数联合血清CXCL8、IL-1β、IL-10诊断乳腺癌的价值研究

目的探讨超声血流参数联合血清趋化因子配体8(CXCL8)、白细胞介素-1β(IL-1β)、白细胞介素-10(IL-10)诊断乳腺癌的价值。方法回顾性分析2021年1月—2023年1月三亚中心医院收治的170例乳腺癌患者的临床资料,将其作为乳腺癌组。另取同期该院170例乳腺良性肿瘤患者作为良性组。比较两组超声血流参数[搏动指数(PI)、阻力指数(RI)]及血清CXCL8、IL-1β、IL-10水平,比较不同临床病理特征乳腺癌患者的PI、RI、CXCL8、IL-1β、IL-10水平,绘制受试者工作特征(ROC)曲线分析PI、RI、CXCL8、IL-1β、IL-10单独及联合诊断乳腺癌的价值,采用多因素逐步Logistic回归模型分析PI、RI、CXCL8、IL-1β、IL-10与乳腺癌的关系。结果乳腺癌组PI、RI、CXCL8、IL-1β、IL-10水平均高于良性组(P<0.05)。临床分期Ⅲ、Ⅳ期,中低分化,淋巴结转移的乳腺癌患者PI、RI、CXCL8、IL-1β、IL-10水平分别高于临床分期Ⅰ、Ⅱ期,高分化,无淋巴结转移的患者(P<0.05)。ROC曲线分析结果表明,PI、RI、CXCL8、IL-1β、IL-10诊断乳腺癌的敏感性分别为75.3%(95%CI:0.724,0.791)、71.2%(95%CI:0.659,0.748)、82.4%(95%CI:0.792,0.886)、85.9%(95%CI:0.804,0.911)、75.3%(95%CI:0.711,0.789),特异性分别为87.1%(95%CI:0.831,0.902)、88.8%(95%CI:0.833,0.914)、85.9%(95%CI:0.816,0.897)、88.2%(95%CI:0.852,0.916)、89.4%(95%CI:0.847,0.922);PI、RI、CXCL8、IL-1β、IL-10联合诊断乳腺癌的敏感性为87.1%(95%CI:0.825,0.912),特异性为91.8%(95%CI:0.887,0.936),优于各项指标单独诊断。多因素逐步Logistic回归分析结果显示:PI≥1.185[O^R=1.753(95%CI:1.178,2.609)]、RI≥0.745[O^R=1.861(95%CI:1.199,2.889)]、CXCL8≥39.535 ng/mL[O^R=2.017(95%CI:1.288,3.159)]、IL-1β≥4.100 pg/mL[O^R=2.115(95%CI:1.304,3.430)]和IL-10≥31.205 pg/mL[O^R=2.344(95%CI:1.398,3.930)]是乳腺癌发生的危险因素(P<0.05)。结论PI、RI、CXCL8、IL-1β、IL-10对乳腺癌均有一定诊断价值,且联合检测诊断效能更高。

Interleukin-10 Is Expressed in HepG2.2.15 Cells and Regulated by STAT1 Pathway

This study investigated the expression profiles of IL-10 gene in three human hepatoma cell lines including Huh7, HepG2, and HepG2 transfected with a plasmid containing hepatitis B virus （HBV） named HepG2.2.15. RT-PCR analysis demonstrated that IL-10 message RNA was absent in HepG2 and Huh7 cells, whereas it was present in HepG2.2.15 cells, which was consistent with ELISA result. Furthermore, except for lamivudine other antiviral treatments did not significantly decrease the HBV DNA level in HepG2.2.15 cells, while they had different effects on the expression of IL-10 protein, although stimulation by LPS had no significant effect. In addition, except for poly（I：C）, the other treatments decreased the expression of IL-10 protein to different degrees, but had no sig-nificant effects on the expression of NF-κB and MyD88. Meanwhile, all treatments we used had effect on the expression of STAT1. In conclusion, IL-10 was expressed in HepG2.2.15 cells and STAT1 pathway might be involved in the regulation of IL-10 expression in HepG2.2.15 cells, but it was not the sole pathway, the exact mechanism warrants further study.

脾气虚型免疫性血小板减少症小鼠模型与白细胞介素-27、白细胞介素-10的表达

目的:研究脾气虚型免疫性血小板减少症(ITP)模型小鼠血清与脾脏组织中白细胞介素-27(IL-27)、白细胞介素-10(IL-10)的表达水平及意义。方法:24只白变种实验小鼠以区间分组法随机分为对照组、模型组、泼尼松组、健脾益气摄血组。除对照组外,其余组均以被动免疫造模法建立脾气虚型ITP小鼠模型。造模后,模型组、对照组用生理盐水灌胃,泼尼松组、健脾益气摄血组分别用泼尼松、健脾益气摄血颗粒灌胃。各组均灌胃1次/d,连续8 d。采用酶联免疫吸附试验检测外周血中血小板计数及血清与脾脏中IL-27、IL-10表达水平。结果:与对照组比较,模型组血清和脾脏IL-27、IL-10均显著降低(均P<0.01)。与模型组比较,泼尼松组、健脾益气摄血组血清和脾脏IL-10均明显升高(P<0.05);泼尼松组、健脾益气摄血组血清与脾脏IL-27均有所升高,但差异均无统计学意义(均P>0.05)。结论:IL-27、IL-10可能在脾气虚型ITP中发挥保护性作用,且发挥作用的主要场所在外周血而非脾脏;此外泼尼松与健脾益气摄血颗粒治疗ITP的机制可能与提高IL-10的含量有关,而与提高IL-27的含量关系不大。

Effects of Micronutrients on Oxidative Stress and Islet Function in Type 1 Diabetes Mellitus Rats:Relationships to Th2 Type Cytokines,Interleukin-4,and Interluekin-10

To observe the effects of the micronutrients on oxidative and autoimmune destruction of islets so as to prevent a person from the onset and development of type 1 Diabetes Mellitus （T1DM）, the interleukin-4 and interleukin-10 expressions of lymphocytes in peripheral blood and spleen of T1DM rats were determined by flow cytometry. GSH-Px activity and MDA level in the rats＇ pancreas were measured using biochemical methods. The insulin contents in serum and β cell insulin secret storage were tested by RIA and IHC, respectively. There was an increase in the percentages of IL-4 and IL-10 positive lymphocytes in the peripheral blood and spleen of the groups of rats supplemented with various combinations of micronutrients（p 〈0.01 and p 〈0.05, respectively） ; the blood glucose concentration decreased （p 〈 0. 05 ） ; both the functional β cell in islets and the insulin content in pancreatic tissue increased （p 〈 0. 05 and p 〈0. 01 ） ; the GSH-Px activity and MDA level of pancreas in the rats enhanced and decreased respectively（p 〈0. 01 and p 〈 0. 05）. The results suggest that micronutrients may alleviate the islet lesions by upregulating the expressions of IL-4 and IL-10 and lowering oxidative stress in diabetic rats .