癌症患者外周血T淋巴细胞丝裂原反应性和血浆IL－2、IL－6活性及IL－2受体的表达

要本文应用生物学测定法检测了肝癌、胃癌、大肠癌、喉癌、乳腺癌外周血Ｔ淋巴细胞丝裂原反应性和血浆ＩＬ－２、ＩＬ－６活性及ＩＬ－２受体的表达。结果表明：各组癌症患者Ｔ淋巴细胞丝裂原反应性和血浆ＩＬ－２、ＩＬ－６活性均显著低于对照组，而ＩＬ－２Ｒ表达却显著高于对照组。各组癌症之间上述各项指标比较均无明显差异。结果提示，癌症患者外周血Ｔ细胞功能被严重抑制，ＩＬ－２、ＩＬ－６和ＩＬ－２Ｒ可能在该病的发病机制中起一定作用     

慢性活动性乙型肝炎患者细胞免疫功能检测及其临床意义

测定了例慢性活动乙型肝炎患者外周血单个核细胞（ＰＢＭＣ）产生的白细胞介素２（ＩＬ－２）活性，其中部分病人检测了血清可溶性白细胞介素２受体（ｓＩＬ－２Ｒ）水平，膜白细胞介素２受体（ｍＩＬ－２Ｒ）表达，ＬＡＫ活性及外周血Ｔ淋巴细胞亚群，并分析了它们之间的相关性，结果表明：ＩＬ－２活性，ｍＩＬ－２Ｒ表达，ＬＡＫ活性，ＣＤ４／ＣＤ８比值显著低于正常对照组（Ｐ〈０．００１），而ｓＩＬ－２Ｒ水平，ＣＤ８细胞显     

细胞因子水平与晚期胃癌患者治疗及预后相关研究

本文报道了２４９例晚期胃癌（Ⅲ～Ⅳ期）患者外周血单个核细胞（ＰＢＭＣ）产生ＩＬ－２水平及ＩＬ－２Ｒ表达，外周血清中ｓＩＬ－２Ｒ浓度与ＰＢＭＣ被ＰＨＡ－Ｐ诱生后产生ＩＦＮ－γ活性；并探讨了姑息性手术、化疗和中药治疗对晚期胃癌患者细胞免疫调节因子水平的影响。结果发现：晚期胃癌患者外周血ＰＢＭＣ产生ＩＬ－２及ＩＦＮ－γ能力及ＩＬ－２Ｒ表达均显著低于早期胃癌患者和正常对照组水平（Ｐ＜０．０１）；ｓＩＬ－２Ｒ水平前者明显低于后二者（Ｐ＜０．０１）。姑息手术治疗尽管对晚期胃癌患者的ＩＬ－２、ＩＬ－２Ｒ和ＩＦＮ－γ水平无显著影响，但可降低其ｓＩＬ－２Ｒ水平；而扶正抗癌冲剂则可是显著提高患者术后ＩＬ－２及ＩＦＮ－γ水平和ＩＬ－２Ｒ表达，同时降低ｓＩＬ－２Ｒ水平（Ｐ＜０．０１）；化疗有效晚期患者，则可导致其ｓＩＬ－２Ｒ水平下降，无效者则ｓＩＬ－２Ｒ水平无改变或继续升高。三年随访发现，晚期胃癌患者，术前ＩＬ－２产生水平高于１００Ｕ／ｍｌ，同时ｓＩＬ－２Ｒ水平低于１０００Ｕ／ｍｌ者，其三年生存率高。因而，这项研究对晚期胃癌治疗疗效判断及预后评价有指导意义。     

IL－2基因转移的瘤苗与IL－1、低剂量环磷酰胺合用后的肿瘤治疗作用及其免疫学机理

经ＩＬ－２基因转移瘤苗治疗后荷瘤小鼠肺转移结节明显减少、存活期明显延长，与ＩＬ－１或低剂量Ｃｙ合用后，可使荷瘤小鼠的肺转移结节更少，存活期更长，特别是当ＩＬ－２基因转移的瘤苗、ＩＬ－１、低剂量Ｃｙ三者合用时抗肿瘤转移效果最强。对瘤苗治疗后荷瘤小鼠体内免疫功能的研究表明，小鼠脾脏ＣＴＬ活性、ＮＫ活性、ＩＬ－２导的ＬＡＫ活性均显著增强，脾脏细胞分泌ＩＬ－２和ＴＮＦ水平也显著升高，当与ＩＬ－１、低剂量Ｃｙ合用时，上述抗肿瘤免疫功能升高得更加明显，可见ＩＬ－２基因转移的瘤苗能通过有效地激活体内抗肿瘤免疫功能而具有显著的抗肿瘤转移效果，将其与ＩＬ－１或低剂量Ｃｙ联合应用时抗肿瘤效果更佳，当三者同时合用时抗肿瘤效果最佳。     

ENHANCED ANTITUMOR EFFECTS OF INTERLEUKIN-2 LIPOSOMES IN C57BL/6N MICE WITH B-16 MELANOMA PULMONARY METASTASES

为研究白细胞介素－２（ＩＬ－２）脂质体对小鼠Ｂ－１６黑色素瘤肺转移瘤的抑制效应和对荷瘤鼠脾淋巴细胞增殖的影响，应用改良超声－薄膜法制备ＩＬ－２脂质体；正常及免疫受抑Ｃ５７ＢＬ／６Ｎ小鼠建立Ｂ－１６黑色素瘤肺转移瘤模型，腹腔注射游离ＩＬ－２（０．２×１０４～５×１０４ｕｋｇ－１ｄ－１×１０ｄ）或脂质体包封的ＩＬ－２（０．０４×１０４～１．０×１０４ｕｋｇ－１ｄ－１×１０ｄ）。结果表明：改良超声－薄膜法制备的ＩＬ－２脂质体为直径２００～２５００ｎｍ的大单层脂质体，包封率４８．２％，具有良好的稳定性。ＩＬ－２脂质体可使荷瘤鼠肺湿重下降０．４％～１３．１％，肺转移瘤结节降低２．７％～４３．５％，脾细胞３Ｈ－ＴｄＲ掺入量增加１．０５～１．９０倍，其作用效应相当于５倍量的游离ＩＬ－２，且对免疫受抑荷瘤鼠的作用更强。提示ＩＬ－２经脂质体包封后，其抑瘤活性和促进淋巴细胞增殖的活性提高约５倍，是一种有希望应用于肿瘤生物治疗的新型制剂。     

慢性乙型肝炎,肝硬化患者外周血LAK细胞活性和sIL—2R测定的意义

采用＾３Ｈ－ＴｄＲ释放法测定５１例慢性肝病患者（ＣＰＨ１０例、ＣＡＨ２３例、ＬＣ１８例）外周血ＬＡＫ细胞活性，并用酶联法测定患者血清中ｓＩＬ－２Ｒ含量；与２９例正常对照组比较，发现肝病患者ＬＡＫ活性降低，ＨＢＶＤＮＡ阳性组ＬＡＫ活性较阴性组低（Ｐ〈０．０５），ｓＩＬ－２Ｒ增高，且慢性肝病组ＬＡＫ活性与ｓＩＬ－２Ｒ水平呈负相关，说明ＬＡＫ活性与机体免疫功能状态有关，ＨＢＶ的复制和高浓度的ｓＩＬ－２Ｒ     

慢性肺心病患者辅以免疫因子治疗前后免疫状态变化观察

对２４例慢性肺原性心脏病急性加重期患者在常规抗感染的同时辅以白细胞介素２（ＩＬ－２）与α－干扰素（ＩＦＮ－α）等免疫因子治疗前后机体免疫状态，包括ＮＫ细胞活性，ＩＬ－２Ｒ阳性细胞比例，可溶性白细胞介素２受体（ｓＩＬ－２Ｒ）的动态变化进行了观察，结果表明，肺心病急性加重期患者ＮＫ细胞活性，ＩＬ－２Ｒ表达的阳性细胞比例均明显低于正常对照组，ｓＩＬ－２Ｒ受体水平明显高于正常对照组（Ｐ〈０．０１）。治疗后     

尿路感染患者血清和尿sIL—2R水平的变化及其意义

应用ＥＬＩＳＡ双抗体夹心法检测尿路感染（ＵＴＩ）患者血清和尿ｓＩＬ－２Ｒ水平。结果显示：①膀胱炎患者血清和尿ｓＩＬ－２Ｒ水平显著低于健康人（Ｐ〈０．０５），提示免疫细胞功能低下可能产ＵＴＩ的易感因素之一。②急性肾盂肾炎（ＡＰＮ）患者血清和尿ｓＩＬ－２Ｒ水平显著高于健康人（Ｐ〈０．０５），提示Ｔ细胞参与了ＡＰＮ机体防御。③慢性肾盂肾炎（ＣＰＮ）患者血清ｓＩＬ－２Ｒ水平显著高于ＡＰＮ组和健康人（分别为     

失血性休克早期白细胞介素1活性变化

观察人血性休克早期大鼠，病人Ｌ－１活性变化，大鼠３０％失血后，腹腔巨噬细胞分泌ＩＬ－１的能力２ｈ内逐渐升高，随后下降，至４ｈ有明显抑制。血浆ＩＬ－１活性于２．５ｈ达高峰值，随后逐渐下降，无应激大鼠及假处理大鼠ＩＬ－１活性均无显著变化。失血性休克患者急诊入院时血浆ＩＬ－１活性也显著升高，与健康志愿者相比差异显著，其机制及意义有待探讨。     

慢性肾炎患者sIL－2R水平、IL－2活性及mIL－2R表达的观察

本文应用ＥＬＩＳＡ法检测了４０例慢性肾小球肾炎血清可溶性白细胞介素２受体水平，同时对患者外周血单个核细胞膜白细胞介素２受体表达及白细胞介素２活性进行观察。结果患者ｓＩＬ－２Ｒ水平为６３４．８±１４２．９ｕ／ｍｌ，高于正常人２９５．０±１６５．７ｕ／ｍｌ，Ｐ＜０．００１；ｍＩＬ－２Ｒ阳性率为２５．６±４．３％，低于正常人４５．５±５．２％，Ｐ＜０．００１；ＩＬ－２活性为２．８５±１．６１ｕ／ｍｌ，低于正常人７．０６±４．５３ｕ／ｍｌ，Ｐ＜０．００１。并且ｓＩＬ－２Ｒ与ＢＵＮ呈正相关，ｒ＝０．４７０，Ｐ＜０．０２。提示慢性肾小球肾炎患者细胞免疫功能降低，且与肾功能损伤程度有关。     

The links between chronic obstructive pulmonary disease and comorbid depressive symptoms: role of IL-2 and IFN-γ

Depression is highly prevalent in COPD patients, and both diseases are believed to be associated with inflammation. The aim of this study was to elucidate the role of the immune system alterations in pathogenesis of depression in COPD patients. Blood was collected from patients diagnosed with chronic obstructive pulmonary disease and comorbid depressive symptoms [COPD + DS, (N = 13)], from individuals with either COPD (N = 16) or recurrent depressive disorder (rDD) alone (N = 15), and from healthy controls (N = 19). Surface phenotype expression of T regulatory and T effector cells was analyzed with a flow cytometry, and IL-2, IL-6, IL-8, IFN-γ, IL-17, and neopterin were detected with ELISA. We demonstrated that COPD, depression, and COPD with comorbid depression are associated with increased IL-6 levels when compared with healthy controls 42.2 ± 1.87, 40.9 ± 2.12, 41.7 ± 1.31, and 33.2 ± 1.23 pg/ml, respectively (p < 0.05). A significant increase in neopterin levels was observed both in rDD and COPD patients when compared with controls (15.69 ± 0.095, 13.98 ± 0.887 vs. 9.22 ± 0.466 nmol/l, p < 0.001 and p < 0.05, respectively). Concentrations of IFN-γ were significantly increased in COPD + DS patients when compared with controls (24.3 ± 1.49 and 17.8 ± 0.70 pg/ml, respectively, p < 0.05). IL-2 levels were highest in COPD + DS (3.20 ± 0.389 pg/ml) and differed significantly when this group was compared with controls (2.20 ± 0.184 pg/ml), p ≤ 0.05). In this study, we demonstrated for the first time that depressive symptoms in COPD patients may be related to inflammatory state as confirmed by increased levels of IL-6 both in COPD and depression and also in COPD with comorbid depressive symptoms, despite the fact that the patients were treated with anti-inflammatory drugs and/or antidepressants. We also identified IFN-γ and IL-2 as putative inflammatory agents associated with depressive symptoms in COPD patients. Prospective studies will need to confirm whether measuring IL-2 and IFN-γ can identify COPD patients at risk of depression. These findings suggest that T helper cell 1-derived cellular immune activation may play significant role in developing depressive symptoms in COPD patients.     

鼻咽癌病人血浆脂质过氧化物,IL—2及IL—2受体活性的研究

本文对不同病期鼻咽癌(NPC)病人血浆中脂质过氧化物—丙二醛(MDA)、外周血淋巴细胞产生IL-2的能力、IL-2受体活性进行初步探讨。结果显示NPC病人血浆中MDA含量较正常人明显增高(P<0.01),晚期病人比早期病人增高更明显(P<0.01);患者外周血淋巴细胞分泌IL-2的能力及IL-2受体活性较正常人明显下降(P<0.01)。这提示了NPC患者血浆中MDA的增高和肿瘤的发生发展有关,NPC患者免疫功能的下降可能与MDA的升高有关。     

Intracellular cytokine profile of T lymphocytes in patients with chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is characterized by an excessive inflammatory response to inhaled particles, mainly tobacco smoking. T lymphocytes are important regulatory cells that secrete several cytokines and participate actively in this inflammatory response. According to the pattern of cytokines secreted, the immune response is classified as cytotoxic or type 1 [interferon (IFN)-gamma-, interleukin (IL)-2-dependent] and humoral or type 2 (IL-4-, IL-5-, IL-10- and IL-13-dependent). This paper sought to compare the intracellular profile of cytokine expression determined by flow cytometry in T lymphocytes harvested from bronchoalveolar lavage (BAL) and peripheral blood in patients with COPD, smokers with normal lung function and never smokers. We found that BAL T lymphocytes from COPD patients had a higher percentage of positive stained cells for most of the cytokines analysed when compared to never smokers or smokers with normal lung function. Differences reached statistical significance for IL-4, IL-10 and IL-13, particularly in CD8(+) T cells. Furthermore, the expression of most of these cytokines was related inversely to the degree of airflow obstruction present suggesting local activation and/or selective homing of T lymphocytes to the lungs in COPD patients. These observations were not reproduced in circulating T lymphocytes. These results suggest that BAL T lymphocytes in patients with COPD produce more cytokines than in controls and tend to show a type 2 pattern of intracellular cytokine expression, particularly a Tc-2 profile. This is related inversely to the degree of airflow obstruction present.     

肾病患者血清IL-8,FN和尿IL-8水平检测的临床意义

目的 :了解肾病患者血清IL - 8、FN和尿IL - 8水平、变化及意义。方法 :采用ELISA夹心法在疾病活动期和激素冲击治疗后 8周测定 5 1例肾病患者血清IL - 8、FN和晨尿IL - 8水平 ,并以 36例随机健康者作比较。结果 :肾病患者血清及尿IL - 8含量显著高于正常人组 (P <0 0 1)但与Scr无显著相关性 (r =0 .12 5 ,P >0 .0 5和r =0 .0 75 ,P >0 .0 5 )而血清FN水平则低于正常人组 (P <0 0 5 )。激素治疗 8周后 ,血、尿IL - 8水平均降低 (P <0 0 5 ) ,血清FN水平有所升高 ,但与治疗前比较无显著差异 (P >0 0 5 )。结论 :IL - 8、FN与肾病的发病机制有关 ,测定血清IL - 8、FN和尿IL - 8有助于判断肾病患者的炎症活动状况 ,有一定的临床价值。     

肝素结合蛋白、1,25-二羟基维生素D3、白三烯B4及炎性指标与慢性阻塞性肺疾病急性加重期患者肺功能的相关性研究

目的 探讨肝素结合蛋白、1,25-二羟基维生素D3、白三烯B4及炎性指标与慢性阻塞性肺疾病急性加重期患者肺功能的相关性研究.方法 选取360例2016年4月至2017年5月期间到我院呼吸科诊治的COPD和AECOPD患者作为研究对象.其中COPD患者167例,作为稳定组,AECOPD患者193例,作为加重组.选取同期进行体检的健康人300例作为对照组.比较3组受试者HBP、1,25-(OH)2D3、LTB4、TNF-α、IL-8和IL-6水平.比较稳定组和加重组肺功能指标.分析HBP、1,25-(OH)2D3、LTB4、TNF-α、IL-8和IL-6与患者肺功能相关性.结果 稳定组、加重组患者HBP和LTB4水平显著高于对照组,1,25-(OH)2D3显著低于对照组,加重组患者HBP和LTB4水平显著高于稳定组,1,25-(OH)2D3显著低于稳定组(P<0.05).稳定组、加重组患者TNF-α、IL-8和IL-6水平显著高于对照组,加重组患者TNF-α、IL-8和IL-6水平显著高于稳定组(P<0.05).加重组患者各肺功能指标(FEV1% Pred、FEV1/Fvc%、MMEF% Pred、V50% Pred、V25%Pred)均显著高于稳定组(P<0.05).经过Pearson相关性分析,HBP、LTB4、TNF-α、IL-8、IL-6与患者肺功能呈负相关, 1,25-(OH)2D3与患者肺功能呈正相关.结论 HBP、1,25-(OH)2D3、LTB4及炎性指标与AECOPD患者肺功能指标密切相关,可以评估患者的病情严重程度,指导临床治疗.     

慢性阻塞性肺疾病T淋巴细胞亚群与生化参数变化及其相关性分析

利用基于免疫荧光标记技术为原理的流式细胞分析技术研究慢性阻塞性肺疾病(COPD)患者免疫功能与生化参数的变化及其相关性分析.对31例COPD患者与30名健康者T淋巴细胞亚群与生化参数等13项指标进行检测,并进行统计学相关分析.结果表明,COPD组和对照组免疫指标比较,CD3 CD4 T淋巴细胞计数无显著性差异(P>0.05),而COPD组中CD3 CD8 T淋巴细胞计数低于对照组(P<0.05),并且CD4/CD8比值升高(P<0.05);COPD组UN、UA、GLU、HDL-C均高于对照组(P<0.05),Cr则明显高于对照组(P<0.01),其余生化参数均无显著性差异(P>0.05);COPD组UA与CD3 CD8 T淋巴细胞呈负相关(r=-0.463,P<0.01),TG与CD3 T淋巴细胞呈负相关(r=-0.493,P<0.01),TG与CD3 CD4 T淋巴细胞呈负相关(r=-0.413,P<0.05).COPD患者的免疫功能与尿酸和血脂水平相关.     

Association of interleukin-8 receptor alpha polymorphisms with chronic obstructive pulmonary disease and asthma

Chronic obstructive pulmonary disease (COPD) and asthma are common complex diseases characterized by airflow obstruction and inflammatory processes in the small airways. lnterleukin 8 (IL-8) is a potent proinflammatory cytokine which interacts with the IL-8 receptor alpha (IL8RA, CXCR1) and beta (IL8RB, CXCR2), leading to activation and migration of leukocytes. In order to evaluate the role of the IL8RA gene in the pathogenesis of COPD and asthma, we screened the coding region of IL8RA for mutations by means of single-strand conformation polymorphism analysis in 50 COPD patients and identified three exchanges (M31R, S276T and R335C). These three polymorphisms were subsequently genotyped in 182 adult patients with COPD, 68 adult patients and 130 children with asthma as well as 454 healthy controls. The frequencies of the IL8RA 31R and 335C alleles were significantly increased in patients with COPD and in children with asthma compared to healthy controls (P=0.0073 and 0.023, respectively). Thus, these polymorphisms may play a role in the pathogenesis of COPD and asthma.     

Imbalances Between Interleukin-1 and Tumor Necrosis Factor Agonists and Antagonists in Stable COPD

Introduction  Interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNFα) are potentially important in Chronic Obstructive Pulmonary Disease (COPD), but little is known of the relationships between these cytokines and their antagonists in disease compared with healthy controls. It is unclear if concentrations relate to disease severity. The study aimed to investigate these relationships and to assess the potential activity of each cytokine in the context of their antagonists. Methods  Plasma cytokines, soluble receptors, and cell counts were measured in patients with stable COPD and age-matched healthy controls (n = 15 for both) daily for 5 days; these mediators were also measured in corresponding sputum samples from the COPD patients. Results  COPD patients had significantly reduced concentrations of the antagonists, IL-1sRII, and IL-1RA compared with controls. In COPD, IL-1β exceeded its antagonists and correlated significantly with BMI and FEV1, while plasma IL-1RA correlated positively with BMI but negatively with sputum IL-1β, neutrophil, and macrophage counts and smoking history. TNFα antagonists exceeded agonists in both groups and did not correlate with COPD severity. Conclusions  Endogenous IL-1β antagonists appear reduced in COPD. Furthermore, IL-1β correlated with clinical aspects of disease severity, suggesting that IL-1β may play a critical role in COPD. Given the relevant concentrations and binding affinities, it is likely that TNFα has limited activity in stable COPD.     

Induced sputum and bronchial mucosal expression of interleukin-13 is not increased in chronic obstructive pulmonary disease

Background:  The Th2 cytokine interleukin-13 (IL-13) has been implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). We sought to examine IL-13 expression in COPD subjects in induced sputum and bronchus specimens. We hypothesized that inflammatory cells expressing IL-13 localize to the airway smooth muscle bundle and bronchial glands.
Methods:  Interleukin-13 was measured in sputum samples from subjects with COPD ( n  = 34) across a range of severity (Global initiative for chronic Obstructive Lung Disease 2–4) and controls ( n  = 14) using ELISA. IL-13+ cells and inflammatory cells were enumerated within surgically resected proximal airway using immunohistochemical techniques from subjects with COPD ( n  = 10), smoking ( n  = 10) and nonsmoking controls ( n  = 8).
Results:  Sputum IL-13 was measurable in only 6/34 subjects with COPD and was not found in the smoking or nonsmoking control subjects. In subjects with COPD and controls there was a paucity of IL-13+ cells. The distribution of inflammatory cells within different airway compartments was similar in COPD and controls except for an increase in CD3⁺ lymphocytes within bronchial glands in COPD ( P  = 0.04).
Conclusions:  Our findings do not support a role for IL-13 in COPD. However, the tissue localization of inflammatory cells to airway compartments, particularly the increase of T cells in glands in COPD may be important in disease.     

慢性阻塞性肺疾病合并2型糖尿病的老年患者肺功能、免疫失衡研究

目的 探讨慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)合并2型糖尿病(type 2 diabetes mellitus,T2DM)老年患者的肺功能、免疫水平变化及其临床意义.方法 选取北京市垂杨柳医院2015年1月至2016年1月收治的120例COPD患者进行研究,其中合并T2DM患者48例(T2DM组)、单纯COPD患者62例(单纯COPD组),比较两组患者肺功能、免疫指标的差异.结果 T2DM组的CD3+、CD4+、CD4+/CD8+测定值均低于单纯COPD组患者(t=4.209、t=4.598、t=5.617,P<0.05),T2DM组CD8+测定值高于单纯COPD组(t=4.157,P<0.05);T2DM组的血清IFN-γ、IL-10的水平均显著的低于单纯COPD组患者(t=4.839、t=8.529,P<0.05),T2DM组的血清IL-4、IL-8的水平高于单纯COPD组(t=4.209、t=4.517,P<0.05);T2DM组的用力肺活量(forced vital capatiry,FVC)、用力呼气容积(forced expiratory volume in 1 second,FEV lung for carbon monoxide,DLCO)水平均显著的低于单纯COPD组患者(t=3.006、t=5.966,t=6.210,P<0.05).结论 老年COPD合并T2DM患者的肺功能损害更加严重,可能与炎症反应水平增强及免疫失衡有关.