Analysis of the Role of D-Dimer,Interleukin-6,and Interleukin-18 in Differential Diagnosis of Pediatric Refractory Mycoplasma pneumoniae Pneumonia

Objective:To analyze the value of D-dimer(D-D),interleukin-6(IL-6),and IL-18 in the differential diagnosis of children with refractory Mycoplasma pneumoniae pneumonia(RMPP).Methods:The medical records of 92 children with Mycoplasma pneumoniae pneumonia(MPP)treated in the hospital were selected for retrospective analysis from January 2023 to January 2024.After comprehensive examinations such as computed tomography examination of the chest,48 children with general Mycoplasma pneumoniae pneumonia(GMPP)were put in the GMPP group and 44 children with RMPP were grouped in the RMPP group.The IL-6,IL-18,and D-D levels were compared between the two groups,and the receiver operating characteristic(ROC)curves were plotted to analyze their value for differential diagnosis of RMPP.Results:The levels of IL-6,IL-18,and D-D in the RMPP group were higher than those in the GMPP group(P<0.05);the ROC curves showed that the specificity of the differential diagnosis of IL-6,IL-18,and D-D was higher,and their diagnostic value was significant.Conclusion:Determination of IL-6,IL-18,and D-D levels in children with MPP can further diagnose the children’s condition,which can help physicians formulate targeted treatment plans,and is of great significance to the improvement of the children’s condition,which is worthy of attention.

顺铂诱导肾损伤模型在C57BL/6小鼠J和N亚型中的差异性研究

目的探讨C57BL/6 J和N亚型小鼠在顺铂诱导肾损伤模型中的易感性差异,为选择药物肾损伤模型提供理论依据。方法雄性C57BL/6小鼠J和N两种亚型,各随机分为正常组(Control)、模型组(cisplatin,CDDP)。模型组腹腔注射顺铂(3.33 mg·kg^(-1)),隔天给药,持续2周,记录小鼠体重变化、存活率;检测Scr、BUN和β2-MG评价肾功能;HE、Masson和PAS染色法观察肾皮质病理改变。IL-6、IL-1β和IL-18等炎症因子检测顺铂导致的肾脏炎症反应。结果与Control组相比,CDDP组两种亚系小鼠Scr、BUN和β2-MG均明显升高;组织学结果显示肾小管损伤,胶原纤维化和糖原沉积均增加;IL-6、IL-1β和IL-18炎症因子含量和肾皮质蛋白表达均明显升高。C57BL/6N与C57BL/6J系小鼠比较,C57BL/6N系小鼠肾功能指标Scr和BUN均值明显偏高(P<0.01),组织学评分各病理损伤较C57BL/6J亚系小鼠明显偏高,反映纤维化的Masson染色差异具有统计学意义(P<0.01);IL-6、IL-1β和IL-18均值明显偏高,但差异无统计学意义。结论C57BL/6 J和N亚型小鼠均可使用顺铂诱导成功肾损伤模型,相比于C57BL/6J小鼠,C57BL/6N亚系小鼠在肾功能、组织学以及炎症因子等方面损伤明显,提示C57BL/6N亚系小鼠更适于作为药物或者其他肾功能损伤模型的建立。

血清中Interleukin-18含量的检测对结肠癌预后判断的价值

目的 探讨结肠癌患者血清中白细胞介素 18(IL 18)水平与预后的关系。方法 收集 10 6例结肠癌患者和 60例健康成人的血清 ,采用酶联免疫吸附反应 (ELISA )检测IL 18的水平。结果 1997年 6月及以前的血清 5 9份 ,IL 18的平均含量为3 3 8.46pg/ml ;1997年 6月以后的血清 47份 ,IL 18的平均含量为 3 2 8.85 pg/ml ;2组比较无显著性差异 (P <0 .0 5 ) ;结肠癌组患者血清IL 18的含量 ( 3 46.5 3 pg/ml± 3 1.2 3pg/ml)明显高于正常对照组 ( 2 3 3 .3 2 pg/ml± 2 2 .5 4pg/ml) ,有显著性差异 (P <0 .0 5 ) ;Ⅱ期、Ⅲ期和Ⅳ期患者血清中IL 18水平明显高于对照组 (P <0 .0 5 ) ,血清IL 18≥ 3 46pg/ml组的患者 5年生存率为 5 .3 % ,血清IL 18<3 46pg/ml的患者 5年生存率为 18.6% ;两组比较有显著性差异 (P <0 .0 5 ) ;多因素分析表明 ,血清IL 18含量是判断结肠癌患者预后的独立因素。结论 血清中IL 18含量与结肠癌患者 5年生存率有密切相关。血清中IL

天水106份冬小麦品种（系）Yr18基因和1BL/1RS易位的分子检测

选用与Yr18基因和1BL/1RS易位系紧密连锁的SCAR和STS标记,对天水106份供试冬小麦育成品种(系)Yr18基因、1BL/1RS易位系的分布情况进行分子检测。结果表明,106份材料中,有2份材料检测到Yr18基因,有55份材料检测到1BL/1RS易位系,分别占被检测材料的1.89%、51.89%。对目前流行条锈菌小种有良好抗性且表现慢锈性的Yr18基因在甘肃天水小麦育种中的利用率较低,而1BL/1RS易位系的利用率仍然较高。品系15-16H307和07-144-2-1-1-1同时检测到1BL/1RS易位系和Yr18基因,建议在甘肃天水小麦抗条锈病育种中合理应用。

ILTV Glycoprotein B(gB)与鸡Interleukin-18(IL-18)真核双表达载体的构建及表达

将ILTVgB基因和鸡IL-18基因插入到真核双表达载体pIRES中,构建共表达gB和IL-18基因的重组质粒pIRES-gB/IL18和表达gB基因的pIRES-gB质粒。通过脂质体将其转染鸡胚成纤维细胞,利用RT-PCR及间接免疫荧光检测重组质粒在体外的表达。将重组质粒通过腿部肌肉多点注射免疫21日龄雏鸡,应用ELISA和流式细胞仪分别检测免疫鸡的体液免疫及细胞免疫水平。结果显示,pIRES-gB/IL18和pIRES-gB转染细胞中分别含gB/IL-18基因的mRNA和gB基因的mRNA。间接免疫荧光检测表明,pIRES-gB/IL18和pIRES-gB在CEF细胞中有效地转录并表达gB蛋白。pIRES-gB/IL18和pIRES-gB免疫雏鸡后均能促进外周血T淋巴细胞亚群数量和血清中特异性抗体水平的增加,但前者的免疫效果明显优于后者,表明gB基因和鸡IL-18基因均获得了表达,且鸡IL-18能明显增强ILTV DNA疫苗诱发的免疫应答。

Association of polymorphisms of interleukin-18 gene promoter region with chronic hepatitis B in Chinese Han population

AIM: To investigate the polymorphisms of interleukin-18 (IL-18) gene promoters, and to disclose whether such polymorphisms are associated with susceptibility to chronic hepatitis B in Chinese Han population. METHODS: Using polymerase chain reaction with sequence specific primers (PCR-SSP) method, the single nucleotide polymorphisms (SNPs) of the promoter region of IL-18 gene at position -607 and -137 were detected in 231 patients with chronic hepatitis B and 300 normal controls. RESULTS: Allele C at position -607 in the promoter of IL-18 gene was detected in 48.7% of normal controls and 51.9% of patients, while allele A at position -607 was detected in 51.3% of normal controls and 48.1% of patients. The frequencies of -607CC, -607 CA and -607AA genotypes in normal controls were 22.0%, 53.3% and 24.7% respectively and in chronic hepatitis B patients were 26.8%, 50.2% and 23.0% respectively. Allele G at position -137 in the promoter of IL-18 gene was detected in 82.3% of normal controls and 88.5% of chronic hepatitis B patients, while allele C at position -137 was detected in 17.7% of normal controls and 11.5% of patients. The frequencies of -137GG, GC and CC genotype were 67.3%, 30.0% and 2.7% in normal controls respectively, while in chronic hepatitis B patients were 78.8%, 19.5% and 1.7% respectively. The frequency of-137GG genotype in chronic hepatitis B groups was significantly higher than that in normal controls (x2=8.55, P=0.003 <0.05), whereas the frequencies of -607C/-137C and -607A/-137C haplotypes in chronic hepatitis B groups were significantly lower than that in normal controls. The association between genotypes of IL-18 promoter region polymorphisms and HBV copies showed that the frequency of -607AA genotype in high HBV-DNA copies groups was lower than that in low HBV-DNA copies groups (x2=6.03, P=0.014 <0.05). CONCLUSION: The polymorphisms of the promoter region of IL-18 gene at position -607 and -137 are closely associated with susceptibility to chronic hepatitis B. The people with allele C at position -137 in the promoter of IL-18 gene may be protected against HBV infection; moreover AA genotype at position -607 may be closely linked to inhibit HBV-DNA replication. These findings give some new clues to the study of pathogenesis of chronic hepatitis B.

Expression and significance of intratumoral interleukin-12 and interleukin-18 in human gastric carcinoma

AIM: To explore the effect of intratumoral expressions of interleukin-12 (IL-12) and interleukin-18 (IL-18) on clinical features, angiogenesis and prognosis of gastric carcinoma. METHODS: The expressions of IL-12 and IL-18 from 50 samples of gastric cancer tissue were analyzed by immunohistochemistry, and microvessel density (MVD) was determined with microscopic imaging analysis system. RESULTS: The positive expression rates of IL-12 and IL-18 were 44% (22/50) and 26% (13/50), respectively. IL-12 was significantly associated with pathologic differentiation, depth of invasion, lymph node metastasis, distant metastasis, and TNM stage, and IL-18 was closely related to distant metastasis. Intratumoral IL-12 and IL-18 expressions were not statistically related to MVD scoring. IL-12-positive patients survived significantly longer than those with IL-12-negative tumors, but there was no significant difference between IL-18-positive patients and IL-18-negative ones. The multivariate analysis with Cox proportional hazard model revealed IL-12, MVD and T stage were independent prognostic factors. CONCLUSION: The positive expressions of IL-12 and IL-18 can play an important role in progression and metastasis of gastric cancer, and IL-12 might be an independent factor of poor prognosis in gastric carcinoma.

Role of serum interleukin-18 as a prognostic factor in patients with hepatocellular carcinoma

AIM:To determine whether serum interleukin-18 (IL-18) levels correlated with clinicopathologic features and prognosis in patients with hepatocellular carcinoma (HCC). METHODS:Serum IL-18,IL-6 and IL-12 levels were measured by enzyme-linked immunosorbent assay (ELISA) from 70 patients with HCC and 10 healthy controls. RESULTS:Serum IL-18,IL-6 and IL-12 levels of patients with HCC were significantly higher that those of the controls. The levels of IL-18 correlated significantly with the presence of venous invasion and advanced tumor stages classified by Okuda's criteria. Patients with high serum IL-18 levels (≥ 105 pg/mL) had a poorer survival than those with low serum IL-18 levels (< 105 pg/mL) (4 and 11 mo,respectively,P = 0.015). Multivariate analyses showed that serum IL-18 level,but not IL-6 and IL-12 levels,was a significant and independent prognostic factor of survival. CONCLUSION:These findings demonstrate that serum IL-8 may a useful biological marker of tumor invasiveness and an independent prognostic factor of survival for patients with HCC. Thus,the detailed mechanisms of IL-18 involving in tumor progression should be further investigated.

Study on interleukin-18 gene transfer into human breast cancer cells to prevent tumorigenicity

To study the effect of interleukin-18 gene transfection on the tumorigenesis of breast cancer cell line Bacp37,human breast cancer cell line Bcap37 were transfected with Lipofectamine and selected by G418.The biological expression of rhIL-18 was tested by RT-PCR and ELISA method;nude mice were injected with Bcap37 cell with or without the hIL-18 gene.The hIL-18 cDNA was successfully integrated into Bcap37 cell; 126.3±4.5pg hIL-18 secreted by one million transduced cells in 24 hours. Nude mice injected with IL-18 gene engineered Bcap37 cell had no tumor growth.These findings indicated that human breast cancer cells were successfully modified by the gene of IL-18 cytokine;the IL-18 gene engineered Bcap37 cells secreted hIL-18 and lost their tumorigenicity.The Bcap37 cells transduced with IL-18 gene may be used as breast cancer vaccine.

Plasma interleukin-18 reflects severity of ulcerative colitis

AIM: The aim of this study was to evaluate the association between ulcerative colitis activity and plasma or mucosal concentrations of interleukin (IL)-18. METHODS: 11-18 concentrations were measured in plasma and mucosal samples from 15 patients with active ulcerative colitis (UC). RESULTS: The mean plasma concentration of IL-18 measured in all patients (422±88 pg/mL) doubled the mean value in healthy controls (206±32 pg/mL); however, the difference was not statistically significant. Plasma IL-18 levels revealed a significant positive correlation with scored endoscopic degree of mucosal injury, disease activity index, clinical activity index and C-reactive protein concentration. The mean concentration of plasma IL-18 was significantly higher in patients with severe ulcerative colitis (535±115 pg/mL) than in patients with mild ulcerative colitis (195±41 pg/mL), and in healthy controls. Although the mucosal mean IL-18 concentration in severe ulcerative colitis (2 523±618 pg/mg protein) doubled values observed in mild one (1347±308 pg/mg protein), there was no statistically significant difference. CONCLUSION: Plasma IL-18 can be considered as a surrogate marker helpful in evaluation of ulcerative colitis activity.

Interleukin-18 genetic polymorphisms contribute differentially to the susceptibility to Crohn's disease

AIM:To investigate the correlation between interleukin-18(IL-18) gene polymorphisms and the risk of developing Crohn's disease(CD).METHODS:The PubMed,CISCOM,CINAHL,Web of Science,EBSCO,Cochrane Library,MEDLINE,EMBASE and CBM databases were searched without any language restrictions using combinations of keywords relating to CD and IL-18 for relevant articles published before November 1st,2013.Screening of the published studies retrieved from searches was based on our stringent inclusion and exclusion criteria and resulted in seven eligible studies for meta-analysis.A metaanalysis was conducted using a random-effects model with STATA 12.0 software.Crude odds ratios(ORs) with95%confidence intervals(95%CI) were calculated.RESULTS:Seven case-control studies,with a total of1930 CD cases and 1930 healthy subjects,met our inclusion criteria.The results of our meta-analysis indicated that the IL-18 rs1946518 A>C and rs187238G>C polymorphisms may correlate with an increased risk of CD under five genetic models(all P < 0.05).Furthermore,we observed positive associations between the IL-18 rs360718 A>C polymorphism and CD risk under three genetic models(C allele vs A allele:OR = 2.03,95%CI:1.20-3.43,P = 0.008;CC vs AA+AC:OR = 2.39,95%CI:1.2-4.43,P = 0.006;CC vs AC:OR = 2.31,95%CI:1.22-4.38,P = 0.010).However,such associations were not found for the IL-18 rs917997 C>T,codon 35 A>C and rs1946519G>T polymorphisms(all P> 0.05).A subgroup analysis was conducted to investigate the effect of ethnicity on an individual's susceptibility to CD.Our results revealed positive correlations between IL-18 genetic polymorphisms and an increased risk of CD among Asians and Africans(all P < 0.05),but not among Caucasians(all P> 0.05).CONCLUSION:This meta-analysis indicated that the IL-18 rs1946518 A> C,rs187238 G>C and rs360718A>C polymorphisms may contribute to susceptibility to CD,especially among Asians and Africans.These polymorphisms are known to reduce IL-18 mRNA and protein levels.

Effect of IL-18 on peripheral blood mononuclear cells of chronic hepatitis B and hepatitis B virus DNA released by HepG2.2.15 cell lines

BACKGROUND: Interleukin-18 (IL-18), a pro-inflamma- tory cytokine that induces interferon-γ (IFN-γ) production in T cells and natural killer cells, plays a critical role in the T-lymphocyte helper type 1 ( Th1) response. This study was designed to explore the effect of IL-18 on peripheral blood mononuclear cells ( PBMCs) derived from chronic hepatitis B (CHB) and on hepatitis B virus (HBV) DNA released by HepG2.2.15 cell lines, which were transfected with hepatitis B virus gene in vitro. METHODS: PBMCs isolated from 25 healthy people and 25 patients with CHB were stimulated with HBcAg and IL-18 of various concentrations for 72 hours. The levels of IFN-γ in the supernatants of cultured PBMCs were determined by ELISA. After the stimulation of IL-18 of various concentra- tions, PBMCs derived from one patient were co-cultured for 96 hours with HepG2. 2. 15 cells which had been cul- tured for 24 hours, and then the supernatants were collected by centrifugation and used for HBV DNA quantitative as- say. RESULTS: When PBMCs were stimulated by HBcAg and IL-18 at various concentrations, the levels of IFN-γ in the supernatants of CHB groups were much higher than those in normal control groups, at 0.2 ng/ml: t =11.70, P< 0.01; at 1.0 ng/ml: t =16.19, P<0.01; and at5.0 ng/ml: t =20.12, P <0.01. In the CHB groups, the levels of IFN-γ in the supernatants of PBMCs stimulated by HBcAg alone were lower than both those stimulated by HBcAg and EL-18 at various concentrations and those stimulated by HBcAg and EL-18 (5.0 ng/ml) together with EL-12 (mild: t = 2.20, P<0.05; moderate; t=2.97, P<0.05; severe; t = 0.66, P >0.05). The content of HBV DNA in the superna- tant of co-cultivation of HepG2. 2. 15 cells and PBMCs without stimulated materials was higher than that stimula-ted by HBcAg and EL-18 at various concentrations of HBc- Ag and IL-18 together with IL-12/IFN-α1lb. CONCLUSION: DL-18 can induce IFN-γ secretion and pro- bably play a key role in the modulation of both innate and adaptive immunity. It has implications in improving im- munoregulatory effect and increasing the ability of immune cells to kill cells infected by virus.

Enhancing cellular immune response to HBV M DNA vaccine in mice by codelivery of interleukin-18 recombinant

Objective:To investigate the effect of interleukin-18 (IL-18) on immune response induced by plasmid encoding hepatitis B virus middle protein antigen and to explore new strategies for prophylactic and therapeutic HBV DNA vaccines.Methods:BALB/c mice were immunized with pCMV-M alone or co-immunized with pcDNA3-18 and pCMV-M and then their sera were collected for analysing anti-HBsAg antibody by ELISA;splenocytes were isolated for detecting specific CTL response and cytokine assay in vitro.Results:The anti-HBs antibody level of mice co-immunized with pcDNA3-18 and pCMV-M was slightly higher than that of mice immunized with pCMV-M alone,but there was not significantly different (P>0.05).Compared with mice injected with pCMV-M, the specific CTL cytotoxity activity of mice immunized with pcDNA3-18 and pCMV-M was significantly enhanced (P<0.05) and the level of IFN-γ in supernatant of splenocytes cultured with HBsAg in vitro was significantly elevated (P<0.05) while the level of IL-4 had no significant difference (P>0.05).Conclusion:The plasmid encoding IL-18 together with HBV M gene DNA vaccines may enhance specific TH1 cells and CTL cellular immune response induced in mice, so that IL-18 is a promising immune adjuvant.

Inhibition of hepatic interleukin-18 production by rosiglitazone in a rat model of nonalcoholic fatty liver disease

AIM:To investigate the effects of rosiglitazone(RGZ) on expression of interleukin-18(IL-18) and caspase-1 in liver of non-alcoholic fatty liver disease(NAFLD) rats.METHODS:Twenty-eight Sprague-Dawley(SD) rats were randomly divided into control,NAFLD,and RGZ treated NAFLD groups.A NAFLD rat model of NAFLD was established by feeding the animals with a high-fat diet for 12 wk.The NAFLD animals were treated with RGZ or vehicle for the last 4 wk(week 9-12) and then sacrificed to obtain liver tissues.Histological changes were analyzed with HE,oil red O and Masson's trichrome staining.Expressions of IL-18 and caspase-1 were detected using immunohistochemical staining and semi-quantitative reverse-transcription polymerase chain reaction(RT-PCR) analysis.RESULTS:The expression levels of both IL-18 and caspase-1 were higher in the liver of NAFLD group than in the control group.Steatosis,inflammation and fibrosis,found in the liver of NAFLD rats,were significantly improved 4 wk after RGZ treatment.The elevated hepatic IL-18 and caspase-1 expressions in NAFLD group were also significantly attenuated after RGZ treatment.CONCLUSION:RGZ treatment can ameliorate increased hepatic IL-18 production and histological changes in liver of NAFLD rats.The beneficial effects of RGZ on NAFLD may be partly due to its inhibitory effect on hepatic IL-18 production.

Enhanced expression of interleukin-18 in serum and pancreas of patients with chronic pancreatitis

AIM： To investigate interleukin-18 （IL-18） in patients with chronic panreatitis （CP）. METHODS： We studied 29 patients with CP and 30 healthy controls. Peripheral blood mononuclear cells （PBMC） were isolated and incubated with 50 mmol/L ethanol, lipopolysaccharide （LPS） （doses 25 g/L, 250 g/L, 2500 g/L） and both agents for 24 h. Levels of IL-18 in the supernatants, and levels of IL-18, IL-12, interferon （IFN）-T and soluble CD14 in the serum were analysed by EI_ISA technique. Expression of IL-18 in PBMC was investigated by reverse-transcription （RT）-PCR. IL-18 protein levels in CP tissue and in normal pancreas were studied by ELISA technique. IL-18 levels in PBMC and pancreatic tissue were determined by Westernblot. Immunohistochemistry for pancreatic IL-18 expression was performed.RESULTS： In patients, IL-18 serum levels were significantly enhanced by 76% （mean： 289.9 ± 167.7 ng/L） compared with controls （mean： 165.2 ± 43.6 ng/L; P 〈 0.0005）. IL-12 levels were enhanced by 25% in patients （18.3 ± 7.3 ng/L） compared with controls （14.7 ± 6.8 ng/L, P = 0.0576） although not reaching the statistical significance. IFN-γ, and soluble CD14 levels were not increased. In vitro, LPS stimulated significantly and dosedependently IL-18 secretion from PBMC. Incubation with ethanol reduced LPS-stimulated IL-18 secretion by about 50%. The mRNA expression of IL-18 in PBMC and the response of PBMC to ethanol and LPS was similar in CP patients and controls. In PBMC, no significant differences in IL-18 protein levels were detected between patients and controls. IL-18 protein levels were increased in CP tissues compared to normal pancreatic tissues. IL-18 was expressed by pancreatic acinar cells and by infiltrating inflammatory cells within the pancreas. CONCLUSION： IL-18 originates from the chronically inflammed pancreas and appears to be involved in the fibrotic destruction of the organ.

Relationship of Serum Interleukin-18 and Interleukin-12 Levels with Clinicopathology in Renal Cell Carcinoma

Objective： To investigate the relationship between serum interleukin-18 and interleukin-12 levels and clinicopathology of renal cell carcinoma. Methods： Peripheral blood samples were obtained from 20 healthy volunteers and 60 patients with renal cell carcinoma before curative surgery. IL-12 and IL-18 levels were determined by enzyme-linked immunosorbent assay. Results： Mean serum IL-12 and IL-18 levels were significantly higher in patients with renal cell carcinoma compared with healthy volunteers （P〈0.05） and mean serum IL-12 and IL-18 levels increased in patients as the pathologic stage progressed. A positive correlation was observed between serum IL-12 and IL-18 levels （P〈0.05）. In patients with renal cell carcinoma, increasing serum IL-12 and IL-18 levels correlated with pathological stage and Fuhrman grade. Conclusion： Serum IL-12 and IL-18 might be useful tumor markers in patients with renal cell carcinoma.

Interleukin-18 Suppresses Angiogenesis and Lymphangiogenesis in Implanted Lewis Lung Cancer

Objective： To investigate the effects of interleukin-18 （IL-18） on implanted Lewis lung cancer in suppressing angiogenesis and lymphangiogenesis. Methods： One week after hypodermic inoculation of Lewis cells, sixteen tumor-bearing syngeneic mice were randomly divided into two groups. The mice in the treatment group （group A） were intraperitoneally injected with the IL-18 and in the control group （group B） were intraperitoneally injected with normal saline for 7 days. The mice were killed on day 19. The morphology of the tumors was studied, the growth curve was described and the tumor inhibition rate was calculated. The numbers of metastasized pulmonary colonies were calculated using hematoxylin-eosin （HE） staining. The vascular endothelial growth factor A （VEGF-A）, vascular endothelial growth factor C （VEGF-C）, microvessel density （MVD） and lymphatic microvessel density （LMVD） in tumor mass were measured by immunohistochemistry staining （IHCS）. Results： In the group A, the tumor volume, tumor weigh, lung metastatic nodules, expression of VEGF-A and VEGF-C, MVD were all decreased significantly （P0.01 or P0.05）. The tumor inhibition rate was 75% and the inhibition rate of lung metastatic nodules was 61%. The LMVD in group A was also lower than group B, but without significant difference （P0.05）. Conclusion： IL-18 could suppress the tumor growth and metastasis of implanted Lewis lung cancer by way of down-regulating VEGF-A and VEGF-C expression, suppressing angiogenesis and lymphangiogenesis.

Interleukin-18 suppresses tumor growth and induces tumor cells apoptosis on implanted Lewis lung cancer

Objective： The aim of our study was to investigate the effects of interleukin-18 （IL-18） on implanted Lewis lung cancer in suppressing tumor growth and inducing tumor cells apoptosis. Methods： One week after hypodermic inoculation of Lewis cells, sixteen tumor-bearing syngeneic mice were randomly divided into two groups. The mice in the treatment group were intrapedtoneal injected with the IL-18, in the control group were intrapedtoneal injected with normal saline. The health conditions of the mice were measured, the morphology of the tumors was studied and the apoptosis of implanted lung cancer cells was detected by TUNEL to evaluated the effects of IL-18. Results： IL-18 had no significant effects on the health condi- tions of the mice, but it could suppress the implanted tumor growth （inhibition rate was 75%） and induce tumor cells apoptosis. Conclusion： IL-18 can suppress the implanted Lewis lung cancer cells by way of inducing tumor cells apoptosis. It could be used as a new strategy for lung cancer.

Interleukin-18 polymorphism as an inflammatory index in metabolic syndrome: A preliminary study

AIMTo assess circulatory levels of interleukin-18 (IL-18) and determine whether the presence of IL-18 promoter polymorphism influences metabolic syndrome phenotypes. METHODSThis study recruited one hundred and eighty individuals divided into three groups with sixty subjects each as: Normal weight (18.0-22.9 kg/m2), overweight (23.0-25.9 kg/m2) and obese (> 26.0 kg/m2) according to South Asian criteria of BMI. Fasting blood glucose (FBG), Lipid profile, insulin, IL-18 and tumor necrosis factor (TNF)α were measured using ELISA kits, whereas low density lipoprotein (LDL)-cholesterol, insulin resistance (HOMA-IR) and insulin sensitivity (QUICKI) were calculated. The body fat percentage (BF) was measured through bioelectrical impedance analysis; waist and hip circumference were measured. Genotyping of IL-18 -607 C/A polymorphism was performed by using tetra-primer amplification refractory mutation system. Student t test, One-way analysis of variance, Hardy-Weinberg equilibrium, Pearson’s χ2 test and Pearson’s correlation were used, where a P value < 0.05 was considered significant. RESULTSIn an aged matched study, obese subjects showed higher levels of FBG, cholesterol, triglycerides and LDL levels as compared to normal weight (P < 0.001). Highest levels of IL-18 and TNF levels were also seen in obese subjects (IL-18: 58.87 ± 8.59 ng/L) (TNF: 4581.93 ± 2132.05 pg/mL). The percentage of IL-18 -607 A/A polymorphism was higher in overweight and obese subjects vs normal weight subjects (P < 0.001). Moreover, subjects with AA genotype had a higher BF, insulin resistance, TNFα and IL-18 levels when compared with subjects with AC (heterozygous) or CC (wild type) genotypes. However, we did not find any difference in the lipid profile between three subgroups. CONCLUSIONThis preliminary data suggests that IL-18 polymorphism affects IL-18 levels that might cause low grade inflammation, further exacerbated by increased TNFα. All these increase the susceptibility to develop MetS. Further studies are required to validate our findings.