VEGF, IL-18 and NO production by neutrophils and their serum levels in patients with oral cavity cancer

It is known that the relationship between pro-angiogenic and anti-angiogenic factors is responsible for the presence and intensity of neoangiogenesis. The angiogenic factors are produced by tumour cells and/or by tumour-infiltrating inflammatory cells such as macrophages or polymorphonuclear leukocytes (PMN). In the present study we compared VEGF secretion with IL-18 and NO release by PMN derived from oral cavity cancer patients. Knowledge of the relationship between mediators above could help in better understanding the role of PMN in angiogenesis in this patient group. The results from culture supernatants of PMN were confronted with the serum levels of parameters examined. We found an interesting relationship between VEGF and IL-18 concentrations in the culture supernatants of PMN derived from patients with oral cavity cancer. High production of VEGF was associated with low production of IL-18 by PMN derived from patients before treatment. During examinations after treatment we found lower concentrations of VEGF and higher concentrations of IL-18 than those in the study before treatment. In contrast to VEGF and IL-18, the NO production by PMN of cancer patients, before and after treatment, was unchanged. We also demonstrated markedly elevated serum levels of VEGF as well as IL-18 according to the progression of the disease. Results obtained indicate that relations between VEGF and IL-18 released by PMN may promote neoangiogenesis and may be important for benign tumour cells to acquire metastatic phenotype in the early stage of oral cavity cancer. Furthermore, our results suggest that the concentrations of VEGF and IL-18 in the serum are sensitive tumour markers in this patient group before and after treatment.     

IL-18: relationship with anthropometry, body composition parameters, leptin and arterial hypertension.

OBJECTIVE: Interleukin-18 (IL-18) is a potent pro-inflammatory cytokine with potential atherogenic properties whose role in human obesity has been recently suggested. The aim of our study was to analyze the physiologic distribution of IL-18 among sexes and all decades of the adult life in a healthy population randomly selected and to study its relationship with anthropometric, body composition measurements and leptin concentrations. We also studied the relationship of IL-18 with smoking and arterial hypertension, known risk factors implicated in atherogenesis. MATERIALS AND METHODS: One hundred and thirty four men and 127 healthy women were included in the study. Plasma concentrations of IL-18 and leptin were determined in all subjects. Body composition was evaluated by bioelectrical impedanciometry. RESULTS: IL-18 was distributed similarly in men and women and throughout decades. No significant differences were found in IL-18 between obese and normal-weight men and women according to their body mass index and body fat content. Higher IL-18 concentrations were found in subjects with arterial hypertension. In the bivariate correlation analysis only waist to hip ratio correlated weakly with IL-18 in the whole population (r=0.12, p=0.04). In the multiple regression analysis the relationship between IL-18 and waist to hip ratio lost significance after adjusting for age, sex and body mass index. However, IL-18 remained associated with arterial hypertension (adjusted r2=0.25, p=0.023). CONCLUSIONS: The lack of correlation between IL-18 with anthropometric, body composition variables and leptin in our healthy population argues against a role of this cytokine in obesity. Moreover, our findings suggest the implication of this interleukin in the atherogenic process induced by arterial hypertension.     

Serum nitric oxide metabolite levels in a general healthy population: relation to sex and age

This study aims at determining serum nitrite/nitrate (NO(x)) levels in healthy subjects within the framework of a population-based study. NO(x) concentration was measured in 3505 subjects aged >/=20 years. Subjects with diabetes, renal dysfunction, those undergoing treatment for dyslipidemia and hypertension, were excluded; also excluded were smokers, pregnant women, and subjects with cardiovascular and infectious diseases or cancer; leaving 1983 (667 men, 1316 women) asymptomatic non-smoking subjects for the analysis. NO(x) concentrations were determined in serum and compared in different age groups. Mean+/-SE of NO(x) concentration was 24.8+/-0.02 and 24.4+/-0.01 micromol/l in men and women respectively. Men aged 20-29 years had significantly higher NO(x) levels compared to corresponding women (25.1+/-0.03 vs. 22.7+/-0.02). Serum NO(x) concentration peaked at 50-59 years in both genders. Comparison between lower and upper quartiles of NO(x) levels was performed in both genders. Women with high serum NO(x) were older and had significantly higher body mass index and fasting plasma glucose. The results of this study determine the normal levels of serum NO(x) concentrations in asymptomatic non-smoker subjects; also show that serum NO(x) concentrations indicate sex and age differences in these subjects.     

IL-10 fails to inhibit the production of IL-18 in response to inflammatory stimuli

IL-10 is an inhibitor of the production of pro-inflammatory cytokines such as IL-12 and IL-1beta, but it is not known whether it can inhibit the production of IL-18. Therefore, a variety of in vivo and in vitro models were used to determine whether IL-10 is an inhibitor of IL-18 production. Infection of IL-10-/- mice with Toxoplasma gondii results in increased levels of IL-12 in the serum and in recall responses compared to wild type (WT) mice. Surprisingly, although infection resulted in increased levels of IL-18 in serum, there were no differences between WT and IL-10-/- mice. Moreover, splenocytes from infected WT and IL-10-/- mice produced similar levels of IL-18 and addition of exogenous IL-10 did not inhibit their production of IL-18. To address whether endogenous IL-18 inhibitors were masking increased IL-18 production in the IL-10-/- mice, expression of IL-18 binding protein was examined using RT-PCR. Although infection leads to increased expression of IL-18BP mRNA, no difference was seen between WT and IL-10-/- mice. In addition, splenocytes from IL-10-/- mice produced elevated levels of nitric oxide (NO) compared to WT mice, and NO has been shown to inhibit activity of interleukin-1 converting enzyme (ICE), which is required for IL-18 production. However, the addition of an inhibitor of NO production did not alter the levels of IL-18 produced. Finally, analysis of the levels of cytokine mRNA of macrophages stimulated with LPS and IFN-gamma revealed that although IL-10 is a potent inhibitor of IL-12 mRNA accumulation, it did not inhibit IL-1beta or IL-18. Together, these data indicate that IL-10 is not an inhibitor of the production of IL-18.     

儿童真菌性肠炎患者血清IL-27增高及其意义

目的 评价血清IL-27对儿童真菌性肠炎的诊断价值.方法 收集89例儿童真菌性肠炎,61例儿童病毒性肠炎和41例健康对照者的临床资料及血清.酶联免疫吸附试验(ELISA)检测血清中IL-27和降钙素原(Procalcitionin,PCT)的水平,全自动血球分析仪检测各项白细胞参数,分析IL-27与白细胞计数和PCT的相关性,采用受试者工作曲线(ROC)法评价血清IL-27对儿童真菌性肠炎患者的诊断价值.结果 儿童真菌性肠炎患者血清IL-27水平较儿童病毒性肠炎组和健康对照组显著增高(P＜0.01),儿童真菌性肠炎患者IL-27的水平与白细胞计数无显著相关性(R=-0.198,P＞0.05),与PCT水平呈显著正相关(R=0.419,P＜0.01).IL-27诊断儿童真菌性肠炎的ROC曲线下面积为0.82(95％可信区间:0.63～0.89,P＜0.01).最佳诊断界值为80.5 pg/mL,敏感性为0.75,特异性为0.79.结论 IL-27对儿童真菌性肠炎具有较高的诊断价值.     

Elevated serum level of interleukin (IL)-18, interferon (IFN)-gamma and soluble Fas in patients with pulmonary complications in tuberculosis

Mycobacterium tuberculosis can cause life-threatening complications in which the immune response plays an important role. This study was designed to evaluate the serum levels of interleukin-18 (IL-18), interferon-gamma (IFN-gamma) and soluble Fas (sFas) in cases with pulmonary tuberculosis due to confirmed M. tuberculosis infection. The study comprised 50 patients with M. tuberculosis classified to 13 complicated cases and 37 uncomplicated patients. A significant (P<0.05) increase was found in the serum levels of IL-18, IFN-gamma and sFas in patients compared to controls and also in complicated cases compared to uncomplicated ones. Moreover, a positive significant correlation was found between serum levels of sFas with IL-18 (r=0.532, P<0.001), and with IFN-gamma (r=0.37, P=0.008) and lastly between serum levels of IL-18 with IFN-gamma (r=-0.612, P<0.001). It is concluded from these results with the recent observations that IFN-gamma levels are elevated after successful MTB treatment, suggest the possibility of enhanced Fas expression and then stimulating the infected macrophages to show an increased FasL-induced apoptosis. Modulation of FasL system by M. tuberculosis might represent an escape mechanism to evade the effect of apoptosis. Moreover, the elevated serum levels of IL-18, IFN-gamma and sFas can be considered as pathognomonic markers suggesting pulmonary tuberculosis especially in complicated cases.     

Association of IL-12, IL-18 variants and serum IL-18 with bladder cancer susceptibility in North Indian population

IL-12 and IL-18 are immunomodulatory cytokines that play important roles in host immune response against cancers. Variation in DNA sequence in gene promoter may lead to altered IL-18 production and/or activity, and hence can modulate an individual's susceptibility to BC. To test this hypothesis, we investigated the relationship of IL-18 gene promoter −137 G/C and −607C/A polymorphisms and IL12 (− 16974) A/C with the risk of BC in North Indian population. Polymorphisms in IL-18 and IL-12 genes were analyzed in 200 BC patients and 200 age, ethnicity and sex-matched controls, using restriction fragment length polymorphism-polymerase chain reaction (PCR-RFLP) and amplification refractory mutation specific-polymerase chain reaction (ARMS) method. The concentrations of IL-18 in serum were determined by ELISA. Significant association was observed with IL18 (− 137) G/C heterozygous genotype (GC) with 1.96 folds risk of BC as well at C allele carrier and variant C allele having 2 fold and 1.6 fold risk for BC respectively. IL18 (− 607) C/A, heterozygous CA genotype also showed a high risk (OR = 1.59) for BC. While IL12 (− 16974) A/C heterozygote genotype and C allele carrier demonstrated reduced risk of BC. Hetero genotype of IL18 (− 137) G/C was associated with risk of recurrence (HR = 2.35) in superficial BC patients receiving BCG treatment thus showing least survival. The distributions of IL-18 gene haplotypes were not significantly different between patients and controls. Serum IL-18 levels were significantly higher in BC patients than in the healthy subjects (p = 0.025). Serum IL-18 levels was also significantly associated with IL18 (− 137) G/C in heterozygous genotype (GC) (p = 0.048). Our results suggest that IL-18 gene polymorphism contributes to bladder cancer risk whereas IL-12 is protective. A relation between IL18 (− 137) G/C in heterozygous genotype with elevated IL-18 serum level and bladder cancer risk has been registered in the present study.     

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.     

The effect of weight loss on serum concentration of interleukine-6 (IL-6) and insulin resistance

INTRODUCTION: Interleukine-6 (IL-6) is one of the cytokines, excreting by adipocytes, which increases in obesity. These cytokines participate in very complicated mechanisms of developing insulin resistance that accompany obesity. The aim of the study was to: 1) evaluate the influence of weight loss on insulin resistance and serum concentration of IL-6, 2) evaluate the hypothetical association between serum concentration of IL-6 and the improvement of insulin sensitivity in obese women after weight loss. MATERIAL AND METHODS: The study involved 27 obese women (age 40.3 +/- 11.1 year; BMI 37.4 +/- 5.2 kg/m(2)) with insulin resistance diagnosed using HOMA index, without concomitant diseases and without any medication. All the patients participated in complex weight reduction treatment (diet, physical activity and psychotherapy). Before and after weight reduction therapy weight and height were measured, body composition was determined using bioimpedance analysis. Serum concentration of glucose was determined by enzymatic procedure, serum concentration of insulin was measured by radioimmunoassay, serum concentration of IL-6 was measured by ELISA. HOMA index was calculated with formula. RESULTS: The mean weight loss after 3-month was 9.2 +/- 4.5 kg (approximately 10% of initial weight). After weight reduction significant decreases in HOMA index, insulin and IL-6 concentrations was observed. However, no correlations between changes in insulin concentrations, HOMA index and decrease of IL-6 concentration were showed. We observed significant correlations between DeltaHOMA and DeltaBMI (r = 0.48; p = 0.012) and Delta percentage fat mass (r = 0.39; p < 0.05). CONCLUSIONS: A moderate weight loss improves insulin sensitivity and decreases serum concentrations of IL-6. However improvement of insulin sensitivity is the effect of fat mass reduction and does not change serum concentration of IL-6.     

Blockade of endothelin ET(A)/ET(B) receptors favors a role for endothelin during acute Trypanosoma cruzi infection in rats

Endothelin has been implicated in the pathogenesis of experimental and human Chagas' disease (American trypanosomiasis). In the present study, we tested the effect of bosentan, an antagonist of both ET(A) and ET(B) endothelin receptors, on parasitemia, histopathology (heart and diaphragm), heart levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-10, interferon (IFN)-gamma, CCL2, CCL3 and CCL5, and the serum levels of nitrate/nitrite (NOx). Bosentan treatment was accompanied by a significant increase in parasitemia and tissue parasitism or inflammation. In vehicle-treated rats, Trypanosoma cruzi infection increased the cardiac levels of TNF-alpha, IFN-gamma and IL-10, at day 9 post inoculation, and the TNF-alpha remained elevated until day 13. The infection also caused a significant increase in the cardiac levels of the chemokines CCL2 (9, 13 and 18 days) and CCL3 (13 and 18 days). Bosentan-treatment had no significant effect on the infection-associated increase in IFN-gamma and chemokine concentrations. There was a lower increase in IL-10 at day 9 and this was mirrored by a greater increase of TNF-alpha at day 13, in comparison with vehicle-treated rats. These latter findings correlated well with the enhanced inflammatory process in hearts of bosentan-treated infected rats. Bosentan treatment reduced the infection-associated increase in NOx serum concentration. Altogether, our data suggest that ET action on ET(A) and ET(B) receptors may play a role in the initial control of T. cruzi infection in rats probably by interfering in NO production.     

Relationship Between IL-2, IL-17 Concentrations,and Serum Creatinine Levels in Men with Chronic Kidney Diseases

Background:Chronic kidney disease (CKD), is a major public health challenge worldwide. It is more prevalent in developed countries compared with the rest of the world, due to the higher rates of life expectancy and unhealthy lifestyle related factors. This aim of the current study is to evaluate the relationship between interleukins IL-2 and IL-17 concentrations and kidney function markers in men with CKD.Methods:Forty-five men with CKD and seventy controls were enrolled in the current study to assess the relationship between interleukin-2 (IL-2), interleukin-17 (IL-17), and CKD parameters. Fasting blood samples were collected from patients with CKD and their controls at same time. Serum IL-2, and IL-17 were measured in patients with CKD and their controls, and then the relationship between these interleukins and serum creatinine, serum urea, serum uric acid and urine albumin were evaluated.Results:A significant relationship was detected between IL-2 (p< 0.001), IL-17 (p< 0.001) levels and serum creatinine concentrations. The significant increase of IL-2 and IL-17 levels were also paralleled with a significant increase in serum urea (p< 0.001), and urine albumin (p< 0.001) concentrations respectively.Conclusion:IL-2 and IL-17 may play a critical role in the pathophysiology of CKD. The significant increase of IL-2 and IL-17 is associated with significantly high concentrations of creatinine, serum urea and urine albumin suggesting that these interleukins may be used as targets for future biomarkers and molecular therapy. However, due to limited sample size of the current study, larger prospective cohorts are needed to confirm these observations.Key Words: Chronic kidney disease, Interleukins, Serum creatinine, Serum urea, Urine albumin     

The effect of weight loss on serum concentrations of nitric oxide, TNF-alpha and soluble TNF-alpha receptors

INTRODUCTION: The aims of the present study were to evaluate the effect of weight-loss treatment on serum concentrations of NO and TNF-alpha and to examine whether there is an association between TNF-system activity and serum concentrations of NO after weight loss. MATERIAL AND METHODS: The study group involved 43 obese women (aged 41.8 +/- 11.9 years, weight 95.2 +/- 15.0 kg, BMI 36.5 +/- 4.6 kg/m(2)). The women were subjected to three-month complex weight-loss treatment. Patients were advised to keep to a 1000-1200 kcal diet and to exercise regularly. Pharmacological treatment was not administered. Serum concentrations of nitric oxide metabolites, TNF-alpha and its soluble receptors (sTNFR1, sTNFR2) were measured by ELISA kits; insulin was measured by RIA and glucose, cholesterol, HDL cholesterol and triglicerydes by an enzymatic procedure before and after weight loss. Body composition was determined by impedance analysis using Bodystat. RESULTS: The mean weight loss during treatment was 8.3 +/- 4.3 kg. The serum concentrations of TNF-alpha decreased significantly (p < 0.000) and both receptors sTNFR1 and sTNFR2 increased significantly (p < 0.000) after weight loss. No significant changes in serum concentrations of NO were observed after weight loss. A multiple regression analysis was performed using DeltaTNF-alpha, DeltasTNFR1, DeltaTNFR2 and DeltaNO as dependent variables. A significant correlation was observed between DNO and initial plasma concentrations of TNF-alpha, sTNFR1 and sTNFR2. CONCLUSIONS: This study demonstrates a decrease in serum TNF-alpha concentration as well as an increase in plasma concentration of both TNF receptors but does not show any change in serum concentrations of NO after weight-loss treatment in obese women. It seems that changes in TNF-system activity may be a counter-regulating mechanism, which inhibits further body mass loss. We did not observe any association between changes in TNF-system activity and serum concentrations of NO after weight loss.     

Secreted Respiratory Syncytial Virus G Glycoprotein Induces Interleukin-5 (IL-5), IL-13, and Eosinophilia by an IL-4-Independent Mechanism

The attachment glycoprotein G of respiratory syncytial virus (RSV) is produced as both membrane-anchored and secreted forms by infected cells. Immunization with secreted RSV G (Gs) or formalin-inactivated alumprecipitated RSV (FI-RSV) predisposes mice to immune responses involving a Th2 cell phenotype which results in more severe illness and pathology, decreased viral clearance, and increased pulmonary eosinophilia upon subsequent RSV challenge. These responses are associated with increased interleukin-4 (IL-4) production in FI-RSV-primed mice, and the responses are IL-4 dependent. RNase protection assays demonstrated that similar levels of IL-4 mRNA were induced after RSV challenge in mice primed with vaccinia virus expressing Gs (vvGs) or a construct expressing only membrane-anchored G (vvGr). However, upon RSV challenge, vvGs-primed mice produced significantly greater levels of IL-5 and IL-13 mRNA and protein than vvGr-primed mice. Administration of neutralizing anti-IL-4 antibody 11.B11 during vaccinia virus priming did not alter the levels of vvGs-induced IL-5, IL-13, pulmonary eosinophilia, illness, or RSV titers upon RSV challenge, although immunoglobulin G (IgG) isotype profiles revealed that more IgG2a was produced. vvGs-priming of IL-4-deficient mice demonstrated that G-induced airway eosinophilia was not dependent on IL-4. In contrast, airway eosinophilia induced by FI-RSV priming was significantly reduced in IL-4-deficient mice. Thus we conclude that, in contrast to FI-RSV, the secreted form of RSV G can directly induce IL-5 and IL-13, producing pulmonary eosinophilia and enhanced illness in RSV-challenged mice by an IL-4-independent mechanism.     

Il-4 and IL-13, but not IL-10, protect human synoviocytes from apoptosis

Interleukin-4, which has been contemplated for the treatment of rheumatoid arthritis and/or osteoarthritis because of its anticatabolic properties, has also been shown to modulate apoptosis. Because inadequate apoptosis is thought to contribute to synovial hyperplasia, we have investigated the ability of IL-4 and other Th2 cytokines to protect human synovial cells from apoptosis. Human synoviocytes or synovial explants were pretreated with IL-4, IL-10, and IL-13 before exposure to NO donor sodium-nitro-prusside (SNP). Apoptosis was evaluated by microscopy, annexin V-FITC, 3-(4,5-dimethylthiazol-2-gl)-5-(3-carboxymethoxylphenyl)-2-(4-sulphophenyl-2H: tetrazolium inner salt (MTS) test, pulse field gel electrophoresis, and a method proposed in this study based on (32)P Klenow end labeling of high m.w. DNA. Pretreatment by IL-4 or IL-13, but not IL-10, protected human synoviocytes from apoptosis induced by SNP. Even at doses as high as 2 mM SNP, up to 86% and 56% protection was achieved, after IL-4 and IL-13 treatment, respectively. Cell survival was dependent on IL concentration. IL-4 and IL-13 also had antiapoptotic effects on SNP-treated human synovial explants. Effects of IL-4 and IL-13 varied in the presence of phosphatidylinositol-3 kinase and protein kinase C inhibitors, implying the involvement of these pathways in antiapoptotic signaling. Antiapoptotic effects were dramatically inhibited by LY294002, and partially by the protein kinase C inhibitor G? 6976, while insulin-like growth factor increased synoviocyte survival. The possibility that IL-4 and IL-13 may enhance synovial expansion in vivo by their antiapoptotic effects is discussed.     

IL-18 is correlated with type-2 immune response in children with steroid sensitive nephrotic syndrome

Children with steroid sensitive nephrotic syndrome (SSNS) is thought to have dysregulated type-1/type-2 cytokine network. Interleukin (IL)-18 is a cytokine, which may enhance both type-1 and type-2 responses, depending on the cytokines milieu. This prospective study aimed to assess type-1/type-2 cytokine synthesis and production profile in different stages of SSNS and define the potent involvement of IL-18. Twenty-three children with SSNS, aged 2.5-14 years, were studied; 23/23 both in active stage before treatment initiation and in remission still on steroids; 15/23 in remission off steroids as well. Data were compared with those obtained from 25 age-matched controls. The following parameters were assessed: Basic T cell populations, percentages of CD3+/CD69+/IFN-gamma+ and CD3+/CD69+/IL-4+ T cells as well as serum levels of IFN-gamma, IL-2, IL-4, IL-13 and IL-18. No difference in IL-2 levels was found between nephrotic children of all disease stages and controls (p>0.05). Percentage of CD3+/CD69+/IL-4+ T cells and serum levels of IL-4, IL-13 and IL-18 were significantly higher in the active stage of SSNS compared with the remission stages and controls (p<0.05). On the contrary, percentage of CD3+/CD69+/IFN-gamma+ T cells as well as serum IFN-gamma were significantly lower during active disease stage compared with remission stages and controls (p<0.05). In children with SSNS, of all disease stages, serum levels of IL-18 were significantly correlated with both IL-4 and IL-13 (r=0.628 and p<0.0001, r=0.71 and p<0.0001, respectively). It seems that a type-2 cytokine synthesis and production pattern prevails in children with active SSNS and IL-18 expression is significantly correlated with this type-2 immune response.     

大鼠IgA肾病模型的建立及血清中IL-6、FN、NO的检测

目的建立大鼠IgA肾病（IgAN）模型,测定大鼠血清中的白介素-6（IL-6）、纤维结合蛋白（FN）、一氧化氮（NO）,探讨这些指标水平的变化与IgAN免疫损伤的相关性,为临床治疗提供动物实验研究依据。方法24只大鼠被随机分成3组,每组8只。模型组和治疗组用免疫复合物法复制;正常对照组用生理盐水。10周后,治疗组大鼠被给予雷公藤多甙片3周。留取所有大鼠血清测定IL-6、FN、NO;留取所有大鼠尿液测定红细胞（RBC）、总蛋白量（TPR）;留取所有大鼠肾组织作病理学检查。结果模型组中大鼠尿液中RBC、TPR含量较治疗组及正常对照组显著增高（P〈0．01）;血清中的IL-6、FN的水平较治疗组及正常对照组显著增高（P〈0．01）;血清中的NO水平较治疗组及正常对照组显著降低（P〈0．01）。治疗组的大鼠肾组织病理损伤程度较模型组明显减轻（P〈0．01）。结论血清中的IL-6、FN及NO的水平与RBC数、TPR及肾组织病理损伤程度相关,它们可作为观察IgAN治疗效果的重要指标,也可作为IgAN严重性的预测指标。下调血中的IL-6、FN及上调NO的水平,可减少IgA与FN免疫复合物的形成,从而改善肾组织的免疫损伤。     

重症肺炎患者血清IL-18、IL-23、IL-33与肠道菌群和临床转归的关系分析

摘要 目的：研究重症肺炎（SP）患者血清白细胞介素-18（IL-18）、白细胞介素-23（IL-23）、白细胞介素-33（IL-33）与肠道菌群和临床转归的关系。方法：选取2019年12月～2022年6月济南市人民医院收治的90例SP患者,记作研究组。另取同期收治的90例普通肺炎患者作为对照组。对比两组血清IL-18、IL-23、IL-33与肠道菌群含量,并以Pearson相关性分析两者的关系。此外,将研究组患者按照治疗后临床转归情况的差异分为好转组60例及恶化组30例,多因素Logistic回归分析SP患者临床转归的影响因素。结果：研究组血清IL-18、IL-23、IL-33水平高于对照组（均P＜0.05）。研究组大肠埃希菌、肠球菌含量均高于对照组,而拟杆菌、双歧杆菌及乳酸杆菌含量均低于对照组（均P＜0.05）。经Pearson相关性分析可得：血清IL-18、IL-23、IL-33与大肠埃希菌、肠球菌含量呈正相关关系,而与拟杆菌、双歧杆菌及乳酸杆菌含量呈负相关关系（均P＜0.05）。好转组年龄及血清IL-18、IL-23、IL-33水平均低于恶化组,且机械通气与长期卧床人数占比均低于恶化组（均P＜0.05）。经多因素Logistic回归分析发现：年龄大、机械通气、长期卧床以及血清IL-18、IL-23、IL-33水平高均是SP患者治疗后恶化的危险因素（均P＜0.05）。结论：SP患者血清IL-18、IL-23、IL-33与肠道菌群密切相关,且随着上述三项血清指标水平的升高,患者临床转归越差。     

Cytokine production and killer activity of NK/T-NK cells derived with IL-2, IL-15, or the combination of IL-12 and IL-18

NK cell populations were derived from murine splenocytes stimulated by IL-2, IL-15, or the combination of IL-12 and IL-18. Whereas NK cells derived with the latter cytokines consisted of an homogeneous population of NK cells (DX5+CD3-), those derived with IL-2 or IL-15 belonged to two different populations, namely NK cells (DX5+CD3-) and T-NK cells (DX5+CD3+). Among NK cells, only those derived with IL-12/IL-18 produced detectable levels of cytokines, namely IFN-gamma, IL-10, and IL-13 (with the exception of IL-13 production by NK cells derived with IL-2). As for T-NK cells, IL-2-stimulated cells produced a wide range of cytokines, including IL-4, IL-5, IL-9, IL-10, and IL-13, but no IFN-gamma, whereas IL-15-derived T-NK cells failed to produce any cytokine. Switch-culture experiments indicated that T-NK cells derived in IL-2 and further stimulated with IL-12/IL-18 produced IFN-gamma and higher IL-13 levels. Next, we observed that NK/T-NK cell populations exerted distinct effects on Ig production by autologous splenocytes according to the cytokines with which they were derived. Thus, addition of NK cells derived in IL-12/IL-18 inhibited Ig production and induced strong cytotoxicity against splenocytes, whereas addition of NK or T-NK cells grown in IL-2 or IL-15 did not. Experiments performed in IFN-gammaR knockout mice demonstrated that IFN-gamma was not involved in the killer activity of IL-12/IL-18-derived NK cells. The hypothesis that their cytotoxic activity was related to the induction of target apoptosis was confirmed on murine A20 lymphoma cells. Experiments performed in MRL/lpr mice indicated that IL-12/IL-18-derived NK cells displayed their distinct killer activity through a Fas-independent pathway. Finally, perforin was much more expressed in IL-12/IL-18-derived NK cells as compared with IL-2- or IL-15-derived NK cells, an observation that might explain their unique cytotoxicity.     

早产产妇血清和胎盘IL-17、IL-21及IL-22表达水平与新生儿感染发生的相关性研究

摘要 目的：分析早产产妇血清和胎盘IL-17、IL-21及IL-22表达水平与新生儿感染发生的相关性。方法：选择2020年7月至2021年12月在我院分娩的120例早产产妇作为观察组,另选同期的120例足月分娩产妇作为对照组。检测两组产妇血清和胎盘IL-17、IL-21及IL-22表达水平,根据观察组产妇分娩的新生儿是否发生感染,分为感染组和非感染组,比较两组母体血清和胎盘IL-17、IL-21及IL-22表达水平,使用多因素Logistic回归分析和受试者工作特征曲线(ROC)分析早产产妇血清和胎盘IL-17、IL-21及IL-22与新生儿感染的关系。结果：观察组血清和胎盘IL-17、IL-21及IL-22表达水平均高于对照组（P＜0.05）;感染组母体血清和胎盘IL-17、IL-21及IL-22表达水平均高于非感染组（P＜0.05）;经多因素Logistic回归分析,早产产妇血清和胎盘IL-17、IL-21及IL-22均是新生儿感染发生的独立预测因素（P＜0.05）;经Pearson相关性分析,早产产妇血清IL-17与胎盘IL-17 mRNA、血清IL-21与胎盘IL-21 mRNA、血清IL-22与胎盘IL-22 mRNA均呈正相关（P＜0.05）;经ROC曲线分析,早产产妇血清IL-17、IL-21联合IL-22预测新生儿感染发生的AUC为0.910。结论：早产产妇血清和胎盘IL-17、IL-21及IL-22表达水平升高均与新生儿感染发生密切相关,其中血清IL-17、IL-21联合IL-22预测新生儿感染的效能较高,值得进一步研究应用。