北方汉族人群白细胞介素-6基因-572C/G单核苷酸多态性与冠心病的相关性研究

目的:探讨中国北方汉族人群中白细胞介素-6(IL-6)基因启动子区-572C/G单核苷酸多态性与冠心病的关系。方法:采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法,检测434例冠心病(冠心病组)患者和417名非冠心病人(对照组)的IL-6基因型,探讨-572C/G单核苷酸多态与冠心病的关系。结果:IL-6基因-572C/G多态位点的CC、CG和GG基因型在冠心病组中分别为59.68%、37.09%、3.23%,等位基因频率C和G分别为78.23%、21.77%;在健康成年者中基因型分别为67.87%、30.22%、1.92%,等位基因频率C和G分别为82.97%、17.03%。IL-6基因-572C/G位点多态性在两组人群中的分布差异存在显著性(P<0.05);经Logsitic回归校正性别、年龄、体重指数、高血压病、糖尿病、高胆固醇血症及吸烟等冠心病易患因素后,IL-6基因-572C/G单核苷酸多态是冠心病发病的独立的危险因素(P<0.05);等位基因频率的相对风险分析发现,G等位基因携带者患冠心病的风险是C等位基因的1.356倍〔OR=1.356,95%CI=1.0648～1.7279〕。...     

新疆汉族人群SREBP—1c基因54G／C多态性与急性心肌梗死的相关性研究

目的：探讨固醇调节元件结合蛋白-1c基因18号外显子54G／C基因多态性与新疆地区汉族人群心肌梗死的相关性。方法：采用聚合酶链反应-限制性片段长度多态性方法,对230例急性心肌梗死患者和212例健康受试者SREBP-1c基因18号外显子54G／C位点进行分析,同时进行血糖及血脂水平检测。数据处理利用PEMS for windows3.1软件包完成,用Hardy-Weinberg平衡检验样本的群体代表性,各组基因型和等位基因频率差异比较用x。检验,连续变量的比较用t检验。结果：SREBP-1c基因18号外显子54G／C在病例组和健康对照组中基因型频率分别为：CC型13.04％和4.25％,CG型34．78％和36．32％,GG52．17％和59,43％,两组CC基因型差异具有统计学意义（P〈0.05）,且病例组C等位基因频率高于对照组（P〈0．05）,而GC和GG基因型差异无统计学意义（P〈0.05）。不同基因型间血糖、血脂水平差异具有统计学意义（P〈0．05）。结论：CC基因型和等位基因C可能增加急性心肌梗死发生的风险,并可影响病人的血糖、甘油三酯代谢。     

青霉素过敏人群IL-18血清浓度以及启动子区基因多态性研究

目的：探讨青霉素类抗生素过敏反应与IL-18及其基因多态性的关系。方法：采用ELISA方法检测50例正常对照和67例过敏患者血清中IL-18水平,PCR-SSP法检测IL-18启动子区多态性位点的基因型。结果：青霉素过敏组IL-18血清浓度显著高于正常对照组（P〈0.01）,且随着皮试反应程度的增强,IL-18浓度也随之升高;青霉素过敏病人IL-18-607位点A等位基因出现频率显著高于对照组（P〈0.01）,CA＋CC基因型降低了青霉素过敏发生的风险性[2=5.868,P〈0.05,OR=3.910,95%Cl（1.225,12.478）]。不同基因型患者血清中IL-18浓度无显著性差异。结论：青霉素过敏反应与IL-18升高有关,IL-18基因启动子区-607C/A位点多态性与青霉素过敏显著相关。     

白介素10和白介素17基因启动子区多态性位点与儿童哮喘的相关性研究

目的：探讨IL-10基因启动子区-627A/C和IL-17基因启动子-152A/G位点多态性与儿童哮喘发生的相关性。方法：采用聚合酶链反应-限制性片段长度多态性分析（PCR-PFLP）方法检测186名哮喘儿童、198名健康儿童各个多态性位点的基因型,采用SPSS13.0进行统计学分析。结果：IL-17基因-152A/G位点的基因型及等位基因频率分布在哮喘组与正常对照组均存在显著性差异（p〈0.05）,哮喘组-152A/G位点等位基因A频率显著高于正常对照组（x2=6.077,p=0.014,OR=1.430,95%CI=1.076-1.902）。结论：IL-17基因-152A/G位点可能与儿童哮喘的发病存在关系,其中A等位基因可能是易感基因,携带A的个体可能更易患有哮喘。     

IL-10基因启动子-627位点多态性与过敏性哮喘

目的：探讨白细胞介素-10（IL-10）启动子-627C／A基因多态性和等位基因频率与过敏性哮喘血清IgE、IL-10浓度以及病情严重程度的相互关系。方法：从哮喘病人DNA文库中选择青岛地区过敏性哮喘病人518例和健康志愿者501例,采用PCR—RFLP方法对IL．10基因启动子．627位点多态性进行观察,比较两组基因型和等位基因的分布频率,同时测定血清中总IgE、IL-10浓度和肺功能检查（FEV1、FVC、FEV1／FVC）。结果：轻度和中一重度哮喘组AA、CA和CC基因型所占比例分别为38．1％、46．0％、15．9％和45．6％、46．2％和8．2％（P=0．0168,X2=8．232,df=2）。A等位基因与哮喘病轻的严重程度有明显相关性（P〈0．05）。AA基因型哮喘病人血清的IgE浓度显著升高（P〈0．01）,但其血清IL-10浓度比CC基因型携带者明显降低（P〈0．01）。结论：IL-10基因启动子-627位点多态性与过敏性哮喘的发生有一定的相关性,等位基因A是哮喘患病的风险基因,而等位基因C则是哮喘病的保护基因。     

亚甲基四氢叶酸还原酶基因C677T、G1793A单核苷酸多态性与散发性乳腺癌易感性的关系

目的：研究亚甲基四氢叶酸还原酶（MTHFR）基因C677T、G1793A位点单核苷酸多态性与散发性乳腺癌易感性关系。方法：采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法,对200例乳腺癌患者及200例正常对照者MTHFR基因C677T、G1793A位点单核苷酸多态性进行分析,logistic回归分析不同基因型与乳腺癌风险的关系。结果：乳腺癌组MTHFR 677TT基因型频率为25.00%显著高于正常对照组的10.50%（X2=14.401,P=0.001）,CT基因型频率为44.50%低于正常对照组的54.50%,CC基因型频率在乳腺癌组和正常对照组中无差别;MTHFR 1793GA基因型频率为18.50%显著高于正常对照者的8.50%（X2=8.563,P=0.003）。乳腺癌患者MTHFR 677T和1793A等位基因频率分别为47.25%、9.25%,显著高于对照组中的37.75%、4.25%。MTHFR 677TT基因型携带者罹患乳腺癌的风险是677CC基因型携带者的2.732倍（95%CI=1.418～5.051,P=0.001）,MTHFR1793GA基因型携带者罹患乳腺癌的风险是1793GG基因型携带者的2.444倍（95%CI=1.325～4.505,P=0.003）。另外,乳腺癌组中MTHFR C677T基因多态性与肿瘤大小相关（x2=7.431,P=0.024,MTHFR G1793A基因多态性与淋巴结转移情况（x2=8.939,P=0.011）、癌组织学分级（x2=9.983,P=0.007）相关。结论：MTHFR C677T、G1793A基因多态性与散发性乳腺癌的易感性相关。     

白介素18启动子区基因多态性与儿童EV71感染相关性研究

目的:研究白介素18基因启动子多态性与儿童EV71感染遗传易感性的关系.方法:收集EV71感染患儿177例,单纯HFMD组127例,HFMD并脑炎组50例,提取外周血DNA,用序列特异性引物-聚合酶链反应(SSP-PCR)技术及基因测序法检测IL-18启动子区-137G/C、-607A/C位点的基因多态性.结果:EV71感染患儿与健康儿童IL-18-607基因型以CA为主,AA、CC次之,EV71感染患儿AA基因型、A等位基因分布频率显著高于健康儿童.EV71感染HFMD并脑炎组患儿AA基因型分布显著高于单纯HFMD组患儿,差异有统计学意义.EV71感染患儿与健康儿童IL-18-137基因型以CC为主,CG次之,GG占少数.该位点基因型及等位基因在EV71感染组与健康儿童、单纯HFMD与HFMD并脑炎组的分布无显著差异.结论:IL-18基因多态性与EV71感染相关,IL-18-607AA基因型、A等位基因携带儿童更易感染EV71病毒,且AA基因型患儿易并发脑炎,-607AA基因型可能为EV71感染的易感基因型.-137C/G位点基因多态性与EV71感染无相关性.     

新疆汉族人群SREBP-1c基因54G/C多态性与急性心肌梗死的相关性研究

目的:探讨固醇调节元件结合蛋白-1c基因18号外显子54G/C基因多态性与新疆地区汉族人群心肌梗死的相关性.方法:采用聚合酶链反应-限制性片段长度多态性方法,对230例急性心肌梗死患者和212例健康受试者SREBP-1c基因18号外显子54G/C位点进行分析,同时进行血糖及血脂水平检测.数据处理利用PEMS for windows 3.1软件包完成,用Hardy-Weinberg平衡检验样本的群体代表性,各组基因型和等位基因频率差异比较用x2检验,连续变量的比较用t检验.结果:SREBP-le基因18号外显子54G/C在病例组和健康对照组中基因型频率分别为:CC型13.04%和4.25%,CG型34.78%和36.32%,GG52.17%和59.43%.两组CC基因型差异具有统计学意义(P＜0.05),且病例组C等位基因频率高于对照组(P＜0.05),而GC和GG基因型差异羌统计学意义(P＜0.05).不同基因型问血糖、血脂水平差异具有统计学意义(P＜0.05).结论:CC基因型和等位基因C可能增加急性心肌梗死发生的风险,并可影响病人的血糖、甘油三酯代谢.     

白介素-18 基因多态性与黑龙江省汉族人群心房颤动相关性

目的:探讨白介素-18(IL-18)基因启动子区-137G/C(rs187238)位点和-607A/C(rs1946518)位点的等位基因、基因型、单体型与黑龙江省汉族人群心房颤动发病风险的相关性。方法:选取56例心房颤动患者和26例对照者,心房颤动患者按持续时间分为阵发房颤组和持续房颤组。采用聚合酶链式反应(PCR)和直接测序法(DS)对所选2个SNPs位点的基因型进行检测。结果:1黑龙江省地区汉族人群中IL-18基因启动子区-607A/C位点存在AA、AC、GG三种基因型,-137C/G位点存在CC、GC、GG三种基因型。2各心房颤动患者组与对照组间IL-18基因启动子区-137G/C(rs187238)位点和-607A/C(rs1946518)位点的基因型和等位基因频率比较均无显著性差异(P0.05)。3IL-18基因启动子区-137G/C(rs187238)位点和-607 A/C(rs1946518)位点有CA、CC、GA、GC四种单倍体型,各组单倍体型分布频率比较均无统计学差异(P0.05。4IL-18基因启动子区-137G/C(rs187238)位点和-607 A/C(rs1946518)位点的基因型和等位基因频率与AF患者的发病年龄均无统计学相关性(P0.05)。结论:IL-18基因启动子区-607A/C(rs1946518)位点和-137G/C(rs187238)位点不是黑龙江省汉族人群心房颤动的易感基因,可能与其心房颤动的发病风险无关。     

MTHFR、MTRR和MTR基因多态性与唐氏综合征发生的相关性研究

应用PCR-RFLP方法分析31例唐氏综合征（Down＇s syndrome, DS）患儿母亲和68例正常生育女性叶酸代谢相关基因：MTHFR 677C〉T、MTRR 66A〉G和MTR 2756A〉G多态性,探讨其与唐氏综合征DS发生的关系。采用Pearson χ^2 检验基因和基因型频率分布,并分析各基因之间的相互作用,计算比值比评价相对危险度。MTHFR基因T等位基因频率在病例组和对照组中具有显著性差异（P〈0.05）,而MTRR和MTR基因G等位基因频率在病例组和对照组中的差异无显著性。MTHFR TT基因型母亲生育DS风险显著增加（OR=3.51,95 %CI=1.04-11.85,P〈0.05）。MTRR GG基因型生育DS的风险增加3.57倍（OR=3.57,95 %CI=1.19-10.73,P〈0.05）。MTR突变基因型AG和GG与生育DS的风险无显著关系。MTHFR （CT＋TT）/MTRR GG、MTHFR （CT＋TT）/MTR AA和MTRR GG/MTR AA联合基因型与DS发生风险显著相关。结果表明,MTHFR 677C〉T、MTRR 66A〉G位点变异是生育DS的独立风险因子,尚不能认为MTR 2756A〉G多态与DS发生相关。基因与基因多态位点之间存在交互和修饰效应。     

Sequential measurement of IL-6 blood levels in patients with systemic inflammatory response syndrome (SIRS)/sepsis

This study was undertaken to investigate whether sequential measurement of blood interleukin (IL)-6 levels using chemiluminescent enzyme immunoassay (CLEIA) would be useful for the management of patients with systemic inflammatory response syndrome (SIRS)/sepsis. Forty consecutive patients with SIRS/sepsis admitted to ICU were involved in the study. Blood IL-6 level was measured everyday throughout their ICU stay at the clinical laboratory by CLEIA method. The platelet count and the sequential organ failure assessment (SOFA) score were measured consecutively. The blood IL-6 levels were elevated in SIRS/sepsis patients and were extremely high in patients with septic shock. There was no significant difference in the blood IL-6 level on admission between survivors (n=27) and non-survivors (n=13). However, the mean blood IL-6 level during ICU stay was significantly higher in the non-survivors (p<0.05). There were significant correlation between the peak IL-6 blood level and the lowest platelet count, and between the peak IL-6 blood level and the maximum SOFA score, respectively. The platelet count became lowest 2.0+/-2.0 days later on average, and the SOFA score became maximal 2.5+/-1.4 days later on average following the day when IL-6 reached its peak value. Sequential measurement of blood IL-6 levels by CLEIA is useful in evaluating the severity and in predicting the outcome of the patients with SIRS/sepsis.     

Tumour necrosis factor-alpha (TNFalpha) and interleukin-10 are crucial mediators in post-operative systemic inflammatory response and determine the occurrence of complications after major abdominal surgery

BACKGROUND: The course of serum cytokine levels in patients with postoperative systemic inflammatory response syndrome (SIRS) after major abdominal surgery remains currently unclear. METHODS: Blood was sampled pre- and post-operatively and on days 1 and 2 in 40 patients undergoing major abdominal surgery. Concentrations of tumour necrosis factor-alpha (TNFalpha), interleukin (IL) -6, IL-8, and IL-10 were measured by the LINCOplex assay; those of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) by an enzyme immunoassay. RESULTS: Compared to their pre-operative values, sTREM-1 was elevated on day 2; TNFalpha on day 1; IL-6 and IL-10 post-operatively and on days 1 and 2; and IL-8 post-operatively and on day 1. The duration of operation correlated with TNFalpha and IL-10 at all sampling times, and with IL-6 post-operatively. There were no differences in cytokine concentrations between patients who exhibited post-operative complications and those who did not. IL-10/TNFalpha below 30 was found in all patients with complications (100%) and in 20 patients without complications (64.5%, p: 0.043). CONCLUSIONS: SIRS following major surgery is characterised by complex alterations in cytokine concentrations. The balance between TNFalpha and IL-10 seems to determine the occurrence of post-operative complications.     

IL-27 和PCT 联合检测在不同分型的脓毒症危重患者中的诊断价值

目的：探讨白细胞介素-27（Interleukin 27,IL-27）对成人全身炎症反应综合征（systemic inflammatory response syndrome, SIRS）和脓毒症的诊断价值。方法：214 例SIRS患者按入院诊断结果及感染源不同分为非脓毒症组（n＝80）、肺源性脓毒症组（n＝ 73）和非肺源性脓毒症组（n＝ 61）。采用酶联免疫吸附试验（ELISA）检测各组患者血清IL-27 和降钙素原（PCT）水平;绘制受试者 工作特征曲线（ROC）,判断各指标的诊断价值,分析各生物标志物的性能,判断潜在的预测变量。结果：肺源性脓毒症患者体温符 合SIRS 标准的比例为65.8%,明显高于非脓毒症患者（45.0%）及非肺源性脓毒症患者（45.9%）（P ＜ 0.05）;非肺源性脓毒症患者白 细胞数符合SIRS标准的比例为68.9%,明显高于非脓毒症患者42.5%,（P ＜ 0.05）。确诊脓毒症后的患者血清IL-27 的AUC 为 0.655,PCT的AUC 为0.649。根据不同感染源进一步分析,肺源性和非肺源性脓毒症患者血清IL-27 水平明显高于非脓毒症患 者,肺源性和非肺源性脓毒症患者PCT 水平明显高于非脓毒症患者（P＜0.01）。ROC曲线分析发现,肺源性和非肺源性脓毒症患 者血清IL-27 的AUC分别为0.657 和0.652,肺源性和非肺源性脓毒症患者PCT 的AUC 为0.667 和0.629。分别联合检测三组患 者的血清IL-27 和PCT值,肺源性脓毒症患者的AUC为0.728,非肺源性脓毒症患者的AUC 为0.703。对肺源性脓毒症患者与非 肺源性脓毒症患者诊断的准确性均有所提升。结论：肺源性和非肺源性脓毒症患者较非脓毒症患者更加符合SIRS 标准。IL-27 作 为脓毒症诊断的生物标志物,对病情变化的反应不敏感,而IL-27 和PCT 结合可以使诊断的准确性提高。     

Anti-inflammatory response of IL-4, IL-10 and TGF-beta in patients with systemic inflammatory response syndrome

The systemic inflammatory response syndrome (SIRS) is an inflammatory process seen in association with a large number of clinical infective and non-infective conditions. The aim of this study was to investigate the role of anti-inflammatory cytokines such as interleukin-4 (IL-4), interleukin-10 (IL-10), and transforming growth factor-beta (TGF-beta). Serum levels of IL-4, IL-10 and TGF-beta were determined in 45 patients with SIRS: 38 patients had SIRS of infectious origin, whereas seven patients had non-infectious SIRS. Twenty healthy subjects were used as controls. Serum levels of IL-4, IL-10 and TGF-beta were determined by an immunoenzyme assay. A significant increase of IL-4 was observed in these patients at the time of diagnosis and 5 days later. In contrast, serum levels of IL-10 were not increased at the time of diagnosis, but a slight decrease was noted after 5 days. Serum levels of TGF-beta were not increased at time of diagnosis, and a slight increase was observed after 5 days. Serum levels of IL-4 were significantly higher in patients with infectious SIRS at the time of diagnosis, whereas no significant difference between infectious and non-infectious SIRS was noted for serum levels of IL-10 and TGF-beta at the time of diagnosis and 5 days later. During SIRS, serum levels of IL-4 were significantly increased with a significant correlation between IL-4 and mortality, and only levels of IL-4 were significantly increased in the SIRS caused by infectious stimuli.     

IL-10基因启动子-627位点多态性与过敏性哮喘

目的:探讨白细胞介素-10(IL-10)启动子-627C/A基因多态性和等位基因频率与过敏性哮喘血清IgE、IL-10浓度以及病情严重程度的相互关系。方法:从哮喘病人DNA文库中选择青岛地区过敏性哮喘病人518例和健康志愿者501例,采用PCR-RFLP方法对IL-10基因启动子-627位点多态性进行观察,比较两组基因型和等位基因的分布频率,同时测定血清中总IgE、IL-10浓度和肺功能检查(FEV1、FVC、FEVl/FVC)。结果:轻度和中-重度哮喘组AA、CA和CC基因型所占比例分别为38.1%、46.0%、15.9%和45.6%、46.2%和8.2%(P=0.0168,X~2=8.232,df=2)A等位基因与哮喘病轻的严重程度有明显相关性(P<0.05)。AA基因型哮喘病人血清的IgE浓度显著升高(P<0.01),但其血清IL-10浓度比CC基因型携带者明显降低(P<0.01)。结论:IL-10基因启动子-627位点多态性与过敏性哮喘的发生有一定的相关性,等位基因A是哮喘患病的风险基因,而等位基因C则是哮喘病的保护基因。     

脓毒症患儿内生吗啡动态变化及临床意义

目的:检测脓毒症患儿血清内生吗啡(EM)动态变化,探讨脓毒症患儿血清EM水平的临床意义。方法:选择2017年6月-2018年2月华中科技大学同济医学院附属同济医院收治的30例伴有严重脓毒症或脓毒症休克的患儿作为脓毒症组,30例全身炎症反应综合征(SIRS)患儿作为SIRS组,30例健康儿童作为对照组。脓毒症组、SIRS组及对照组分别于入组后第1、3、6、9天抽取外周静脉血,采用免疫荧光法检测血清降钙素原(PCT)水平,采用酶联免疫吸附试验(ELISA)测定血清EM水平,采用流式细胞术(FCM)检测细胞免疫功能。结果:SIRS组、脓毒症组患儿的第1、3、6天血清PCT水平显著高于对照组,且随时间延长PCT水平逐渐降低,至第9天降至正常水平(P0.05),而脓毒症组与SIRS组间血清PCT水平无统计学差异(P0.05)。脓毒症组第1、3、6天血清EM水平均高于SIRS组(P0.05),第9天两组血清EM水平比较差异无统计学意义(P0.05)。脓毒症组EM水平随时间延长而降低,至第9天降至SIRS组的水平(P0.05)。与SIRS组相比,第1天脓毒症组的CD3~+T细胞数量增多(P0.05),两组CD4~+、CD8~+T细胞数量、CD4~+/CD8~+比例比较无统计学差异(P0.05)。结论:脓毒症患儿中血清EM水平较高,有可能作为诊断脓毒症特异性较高的生物标志物。     

代谢综合症患者血清IL-18 水平变化及临床意义

目的:研究血清IL-18与亚代谢综合症(亚MS)、代谢综合症(MS)的关系,探讨生活方式改变(TLC)后IL-18及相关标记物的变化及其临床意义。方法:16例对照组,14例亚MS组,34例MS组;采用自动生化仪测定空腹血脂水平;采用乳胶增强免疫比浊法检测hs-CRP水平;采用ELISA法检测受试者血清IL-18、IL-6和脂联素水平。结果:MS患者血清IL-18水平与腰围有明显相关性(rs=0.45,P<0.01);与亚MS组比较,MS组IL-18水平显著升高(P<0.01);与正常组比较,MS组患者的腰围、体重指数、hs-CRP、IL-6及IL-18显著升高(P<0.05)。TLC后体重减轻5%,MS患者IL-18、IL-6、hs-CRP水平显著降低(P<0.01),脂联素水平显著升高(P<0.01)。结论:IL-18可作为亚MS和MS预测指标,鉴别亚MS与MS,其含量的变化对病情进展的程度及疗效的判定有重要意义。     

Interleukin-6 as an independent predictor of future cardiovascular events in high-risk Japanese patients: comparison with C-reactive protein

Inflammation is associated with the development of atherosclerotic vascular lesions and some inflammatory parameters are used as cardiovascular (CV) risk markers. The present study was designed to assess the predictive power of interleukin (IL)-6 for future CV events. In 121 Japanese patients with multiple CV risk factors and/or disease, serum concentrations of IL-6 and high sensitive C-reactive protein (hs-CRP) were measured. During follow-up periods (mean, 2.9 years) after the baseline assessment, 50 patients newly experienced CV events such as stroke/transient ischemic attack (n=10), heart failure hospitalization (n=6), acute coronary syndrome (n=7), and revascularization for coronary artery disease (n=15) and peripheral arterial disease (n=12). The serum level of IL-6, but not hs-CRP, was significantly higher in patients who had CV events than in event-free subjects (3.9±2.6 and 3.0±2.2 pg/mL, P=0.04). When the patients were divided into three groups by tertiles of basal levels of IL-6 (<1.85, 1.85-3.77, and ≥3.77 pg/mL), cumulative event-free rates by the Kaplan-Meier method were decreased according to the increase in basal IL-6 levels (65%, 50%, and 19% in the lowest, middle, and highest tertiles of IL-6, respectively; log-rank test, P=0.002). By univariate Cox regression analysis, previous CV disease, creatinine clearance, and serum IL-6 levels were significantly associated with CV events during follow-up. Among these possible predictors, the highest tertile of IL-6 was only an independent determinant for the morbidity in the multivariate analysis (hazard ratio 2.80 vs. lowest tertile, P=0.006). These findings indicate that IL-6 is a powerful independent predictor of future CV events in high-risk Japanese patients, suggesting its predictive value is superior to that of hs-CRP.     

Cytokine and molecular networks in sepsis cases: a network biology approach

Background

Sepsis is a life-threatening condition of organ dysfunction caused by a dysregulated host immune response to infection. We performed network analysis of cytokine molecules and compared network structures between a systematic inflammatory response syndrome (SIRS) or normal control (NC) group and a sepsis group.

Results

We recruited SIRS (n = 33) and sepsis (n = 89) patients from electronic medical records (EMR) according to whether data on PCT, CRP, interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12p70, IL-13, IL-17, IL-22, TNF-α, and IFN-γ levels were available. From the public GEO dataset, GSE66099, GSE9960, GSE95233, GSE57065 were downloaded. Genes corresponding to 15 molecules were extracted from an expression array. A correlation matrix was formed for the 15 molecules and statistically significant molecular pairs were used as pairs for network analysis of coexpression. The number of molecular or gene expression pairs significantly correlated among the SIRS or control and sepsis groups are as follows for datasets: EMR, 15 and 15; GEO66099-1, 13 and 15; GEO9960, 13 and 11; GSE95233, 13 and 8; GSE66099-2, 15 and 14; GSE57065, 14 and 13, respectively. Network analysis revealed that network diameter, number of nodes and shortest path were equal to or lower in the sepsis group.

Conclusions

The coexpression network in sepsis patients was relatively small sized and had lower shortest paths compared with the SIRS group or healthy control group. Cytokines with one degree (k = 1) are increased in sepsis group compared with SIRS or healthy control group. IL-9 and IL-2 were not included in network of sepsis group indicating that these cytokines showed no correlation with other cytokines. These data might imply that cytokines tend to be dysregulated in the sepsis group compared to that of SIRS or normal control groups