Interleukin-18 concentration in the peritoneal fluid correlates with the severity of peritonitis

BACKGROUND: Interleukin (IL)-18 is a novel cytokine that has recently been characterized as an inducer of interferon-gamma (IFN-gamma). The aim of this study was to investigate the clinical significance of peritoneal IL-18 concentrations in patients with peritonitis. METHODS: We measured IL-18, IFN-gamma, and IL-10 concentrations in the peritoneal fluid of 28 patients undergoing laparotomy for peritonitis. Correlations between the peritoneal cytokine concentrations and the severity of illness determined by systemic inflammatory response syndrome (SIRS) criteria, Acute Physiological and Chronic Health Evaluation II (APACHE II) score, peritoneal fluid bacterial culture results, subsequent development of organ failure, and length of hospital stay were assessed. RESULTS: Interleukin-18 concentration was significantly increased in patients who developed SIRS, in those with culture-positive peritonitis, and in those who developed organ failure, as compared with the other patients. Interleukin-10 concentration, which was also significantly increased in patients with culture-positive peritonitis, showed a close correlation with IL-18 concentration. Although a weak correlation was observed between IL-18 and IFN-gamma concentrations, IFN-gamma concentrations did not show any association with patients' clinical parameters. However, the IFN-gamma/IL-18 ratio was significantly lower in patients with an APACHE II >/=10, and in those with culture-positive peritonitis, as compared with the other patients. BACKGROUND: Peritoneal IL-18 concentration increased in response to intraperitoneal bacterial infection and seemed to reflect the severity of peritonitis. However, the capacity of IL-18 to produce IFN-gamma may be altered depending on the severity of peritonitis.     

慢性炎症和T淋巴细胞活性与心绞痛的相关研究

目的测定冠心病心绞痛患者外周静脉血中白细胞介素-18(IL-18)、C-反应蛋白(CRP)浓度及外周血辅助性T淋巴细胞(Th)功能的改变,观察心绞痛与非感染性炎症及细胞免疫功能之间的关系。方法应用酶联免疫吸附法(ELISA)测定外周血清IL-18浓度,速率散射比浊法测量CRP浓度;采用流式细胞分析法检测外周血CD4 细胞内干扰素γ(IFNγ-)和白细胞介素4(IL-4)的表达。同时分离外周血单个核细胞,经植物血凝素刺激培养后,应用ELISA检测培养上清液中IFNγ-和IL-4水平以测定辅助性T淋巴细胞的功能改变。结果与对照组比较,心绞痛组患者炎性因子(IL-18和CRP浓度)和辅助性T淋巴细胞因子(IFNγ-)水平以及IFNγ-/IL-4比值明显高于对照组;IFNγ-染色阳性的细胞占CD4 T细胞的比率为15.34%,明显高于对照组的12.09%。而两组间IL-4水平及IL-4染色阳性细胞比率在两组间未见显著统计学差异。在心绞痛分组中,不稳定型心绞痛(UAP)组的IL-18、CRP、IFNγ-水平以及IFNγ-/IL-4比值明显高于稳定型心绞痛(SAP)组。结论IL-18、CRP、IFNγ-浓度随冠状动脉病变的程度而升高,且与动脉粥样硬化斑块的稳定性有关。提示炎性因子和辅助性T淋巴细胞功能的失调可能参与了心绞痛患者冠脉粥样硬化斑块形成的过程。IL-18与CRP、IFNγ-浓度可能对冠心病心绞痛患者的诊断及预后有重要参考价值。     

强直性脊柱炎患者血清IFN一百的变化

为探讨免疫调节异常在强直性脊柱炎(AS)发病机制中所起的作用,采用酶联免疫法(ELISA)检测35例AS患者的血清IFN—γ百含量,并以30例健康体检者为正常对照。结果显示AS患者血清IFN—γ(33.16±12.23pg/mL)明显低于正常对照组(55.16±30.75pg/mL),差异有显著性意义(P<0.01)。提示T淋巴细胞功能异常可能参与AS的发病过程。     

受者特异性产生干扰素γ细胞与急性移植物抗宿主病的关系

目的研究异基因造血干细胞移植(allo-HSCT)中针对受者特异性产生干扰素γ细胞 (IFN-γ PC)与急性移植物抗宿主病(aGVHD)的关系。方法以37例HLA相合的同胞allo-HSCT患者为研究对象,将移植前供者、移植后患者外周血单个核细胞(PBMNC)分别作为反应细胞(RC),移植前受者PBMNC作为异基因刺激细胞(allo-SC),在混合淋巴细胞反应后用酶联免疫斑点法检测针对受者特异性IFN-γ PC,分析其与aGVHD的关系。结果 allo-HSCT前检测受者特异性IFN-γ PC水平, 移植后发生aGVHD组显著高于无aGVHD组(P<0．01);供者针对受者特异性IFN-γ Pc≥20／2×10~5 RC时,发生Ⅱ-Ⅳ度aGVHD的比例显著高于<20／2×10~5RC组(P<0．05)。aGVHD发生时患者针对移植前受者特异性IFN-γ PC水平显著高于移植前相应供者针对受者的水平(P<0．05);亦显著高于 aGVHD患者针对移植前供者的水平(P<0．01)。移植后14天(+14天)和+28天时,aGVHD组受者特异性IFN-γ PC水平均显著高于无aGVHD组(P值均<0．01)。aGVHD患者经过免疫抑制剂治疗7 d后,受者特异性IFN-γ PC较aGVHD发生时显著降低(P<0．05)。结论受者特异性IFN-γ PC的水平能够反映allo-HSCT前后的同种异体反应,有助于临床aGVHD的预测、诊断和监测。     

鼠伤寒沙门菌感染对小鼠Th1／Th2影响的动态研究

目的研究鼠伤寒沙门菌（STM）感染的临床病理特征、机体在感染后的免疫应答反应特点以及沙门氏菌感染对Th反应平衡的影响,为临床相关疾病预防诊断和治疗提供依据。方法分别建立伤寒沙门菌感染和对照小鼠模型。两组动物在不同时点处死,观察小肠、肝脏、脾脏病理改变,流式细胞仪测量脾脏IFN-γ和1L-4表达,分别代表Th1和Th2细胞,计算Th1／Th2比值。结果感染伤寒沙门菌小鼠的小肠、肝脏、脾脏病理改变严重程度与对照组相比,在3天时最重,持续至第7天恢复到正常水平;小鼠接种鼠伤寒沙门菌后Th1／Th2比值明显升高,细胞分类向Th1细胞漂移,第3天时,Th1／Th2升到最高值,与病理改变程度和感染中毒症状一致。结论小鼠感染鼠伤寒沙门菌后,细胞分类向Th1漂移,产生炎症性损伤。     

Expression of interferon-γ and tumor necrosis factor-α in bone marrow T cells and their levels in bone marrow plasma in patients with aplastic anemia

Immune-mediated stem cell damage has been postulated to be responsible for disease initiation and progression in aplastic anemia (AA). It is hypothesized that T lymphocytes play a major role in destroying the bone marrow (BM) stem cells of AA patients by infiltrating the BM and secreting excessive levels of anti-hematopoietic cytokines, interferon-gamma (IFN-), and tumor necrosis factor-alpha (TNF-). We undertook this study to assess the pathogenic significance of anti-hematopoietic cytokines such as IFN- and TNF- in BM T cells and plasma of AA patients. Significantly elevated levels of IFN- and TNF- were found in the BM plasma of AA patients compared to controls (p=0.05 and 0.006, respectively). Intracellular IFN- and not TNF- in BM CD3⁺ T cells of AA patients was significantly higher compared to controls (p=0.04 and p=0.2, respectively). A follow-up analysis of expression of these cytokines in BM T cells and their levels in BM plasma in five AA patients before and 180 days (6 months) after antithymocyte globulin (ATG) and cyclosporin A (CsA) therapy showed a decline 180 days after therapy compared to pre-therapy. We thus conclude that increased production of both IFN- and TNF- in the BM may contribute to disease pathogenesis in AA and ATG therapy may induce hematological remission by suppressing the elevated levels of IFN- and TNF- in AA BM.     

白细胞介素1β和干扰素γ对小鼠胰岛素瘤βTC-6细胞胰岛素分泌功能的影响

目的探讨炎性细胞因子白细胞介素1β（IL-1β）、干扰素γ（IFN-γ）对小鼠胰岛β细胞株βTC-6胰岛素分泌功能的影响。方法将βTC-6细胞培养于高糖DMEM培养基,48h后换用无糖KRBH缓冲液培养30min,分别于含0、1．38、5．50和11．10mmol／L葡萄糖的KRBH缓冲液中孵育60min,放射免疫法检测细胞上清液中胰岛素水平（GSIS）。在BTC-6细胞中分别加入不同浓度的IL-1β（0．15、1．50μg／L）和（或）IFN-γ（10、100U／m1）,24h后换用无糖KRBH缓冲液培养30min,在含1．38mmol／L葡萄糖的KRBH缓冲液中孵育60min,放射免疫法检测细胞上清液中胰岛素水平。多组间数据比较采用单因素方差分析,两组间数据比较采用t检验。结果βTC-6细胞在1．38mmol／L葡萄糖刺激时胰岛素分泌达高峰,与无葡萄糖刺激时相比差异有统计学意义[（151±14）对（120±4）mU／L,t=-4．215,P=0．006];5．50、11．10mmol／L葡萄糖刺激时胰岛素分泌较1．38mmol／L葡萄糖刺激时明显下降（均P〈0．05）。与单纯1．38mmol／L葡萄糖刺激组相比,IL-1β（0．15μg／L）组[（85．53±5．06）mU／L对（103．11±0．27）mU／L,t=4．897,P=0．039]、IL-1β（1．50μg／L）组[（62．62±0．64）mU／L对（103．11±0．27）mU／L,t=212．66,P〈0．001]葡萄糖刺激下胰岛素分泌水平显著下降,下降程度与IL-1β的剂量呈正相关;与单纯葡萄糖刺激组相比,IFN-γ（100U／m1）组葡萄糖刺激下胰岛素分泌显著下降[（73．2±1．6）对（105．2±1．8）mU／L,t=19．52,P：0．003];与IL-1β（0．15μg／L）组及IFN-γ（100U／m1）组相比,IL-1β联合IFN-γ组葡萄糖刺激下胰岛素分泌显著下降（F=77．38,P〈0．001）。结论IL-1β和IFN-γ对13TC-6细胞的胰岛素分泌功能有抑制作用,且两者间具有协同效应。     

干扰素γ与肝纤维化治疗

干扰素γ(IFN γ)具有很强的抗肝纤维化作用,近年来IFN γ治疗肝纤维化的临床和基础研究已有很大进展,现就此作一综述.     

白细胞介素-18对单个核细胞的调节作用及其机制

背景:白细胞介素(IL)鄄18是一种促炎性细胞因子,对多种免疫反应具有重要调节作用。目的:观察IL鄄18对单个核细胞产生1型辅助性T细胞(Th1)细胞因子干扰素(IFN)鄄γ和IL鄄2的影响,及其对细胞内核因子(NF)鄄κB活化的影响,以揭示IL鄄18对单个核细胞的调节作用及其机制。方法:以不同浓度的IL鄄18或IL鄄18 IL鄄12刺激小鼠脾单个核细胞(SMC),采用逆转录聚合酶链反应(RT鄄PCR)检测IFN鄄γ和IL鄄2mRNA的表达,采用酶联免疫吸附测定检测IFN鄄γ和IL鄄2蛋白浓度,采用凝胶电泳迁移率改变实验(EMSA)检测NF鄄κB的活化。结果:IL鄄18刺激后,SMC培养上清液中的IFN鄄γ蛋白浓度随IL鄄18浓度的增高而相应增高;100ng/mlIL鄄18与不同浓度的IL鄄12共刺激后,IFN鄄γ蛋白浓度随IL鄄12浓度的增高而相应增高,与对照组相比有显著差异(P<0.05)。各刺激组的IL鄄2蛋白浓度与对照组相比均无明显改变(P>0.05)。IL鄄18或IL鄄18 IL鄄12刺激后,SMC中NF鄄κB活化。结论:IL鄄18可单独或与IL鄄12协同诱导单个核细胞分泌Th1细胞因子IFN鄄γ,NF鄄κB活化参与了这一过程的信号转导。