病毒性心肌炎患儿血清IL-6、IL-8和TNF-α水平变化与临床表现及预后的关系

病毒性心肌炎以小儿多见 ,柯萨奇B组病毒 (CoxB )是主要病原。IL 6、IL 8和TNF α是免疫和炎症的重要调节因子。我们采用ELISA测定血清中IL 6、IL 8和TNF α三种因子 ,观察到在病毒性心肌炎的早期 ,IL 6、IL 8和TNF α水平较正常儿水平均显著增高 ,且与临床表现、心电图改变、心肌酶的升高是一致的。这三种因子水平的升高可以作为病毒性心肌炎急性阶段的一个重要指标 ,4周后病情进入恢复期 ,IL 6和TNF α水平已降至正常而IL 8仍显著高于正常 ,说明疾病仍未治愈。因此我们认为IL 8恢复至正常可以作为判断病毒性心肌炎治愈及预后判断的主要指标。     

乳腺癌患者放疗后血清IL-6与可溶性IL-6受体含量增加并与免疫细胞比例相关

目的探讨乳腺癌患者血清白细胞介素6 (IL-6)与可溶性白细胞介素6受体(sIL-6R)水平对放疗后免疫功能的评估价值。方法随机选取术后放疗的55例乳腺癌患者为治疗组、经体检合格的55例正常健康成人为对照组,采用ELISA检测对照组及治疗组患者放疗前后血清IL-6与sIL-6R含量,并以流式细胞术检测治疗组患者放疗前后外周血CD45~+CD19~+ B淋巴细胞、 CD45~+CD3~+CD4~+ T淋巴细胞、 CD45~+ CD3~+ CD8~+ T淋巴细胞及CD45~+CD16~+CD56~+自然杀伤(NK)细胞,比较淋巴细胞亚群与IL-6、 sIL-6R含量的相关性。结果治疗组患者放疗后血清IL-6与sIL-6R含量显著高于放疗前及对照组,且Ⅲ期、Ⅳ期乳腺癌患者IL-6、 sIL-6R含量明显升高。治疗组患者放疗后总T淋巴细胞、 NK细胞比例明显降低, B淋巴细胞比例显著升高,且IL-6、 sIL-6R含量与NK细胞比例呈正相关,与B淋巴细胞比例负相关。结论乳腺癌患者血清中IL-6与sIL-6R水平可作为乳腺癌病程评估和放疗后免疫功能的参考。     

IL-6/IL-6受体与类风湿关节炎关联性研究新进展

IL-6是一种多效性前炎症细胞因子,有多种生物活性,包括介导炎症反应,免疫反应等。IL-6在许多炎症性疾病中高表达,如RA,SLE,Crohn’s病等。IL-6的产生受多种因素的调节如NF-κB,Lin28,let-7 microRNA,IL6阳性反馈环,JunB等。IL-6受体(IL-6R)包括特异性IL-6Rα及IL-6Rβ即IL-6家族成员共有的信号转导蛋白gp130。IL-6可通过两种途径向细胞内传导信号:传统途径及反式信号途径,LMO4可参与反式信号途径的调节。IL-6/IL-6R在T、B细胞的发生中起重要作用。IL-6可抑制Th1、Treg的分化,促进Th2的分化;而且IL-6是CD4+T细胞分化为Th17细胞所必需;在B细胞中IL-6可诱导RAG基因的表达,促进抗体的产生。近年来越来越多的证据表明IL-6/IL-6R与RA存在密切关联性。RA患者血清及滑液中IL-6及sIL-6R的浓度升高,并且IL-6水平与疾病活性及临床表现密切相关,这可以解释RA患者的许多症状。因此可将IL-6信号转导途径相关的分子作为RA的治疗靶点,目前也研制出几种药物,其中之一为抗sIL-6R的人源化抗体Tocilizumab。临床试验中,该药可减轻RA患者的症状,降低疾病活性,可是也带来一定的副作用,这就限制了该药在临床中的应用。正在研制的另一种抗IL-6R的抗体可能为干预RA带来新的希望。     

IL-17在病毒性心肌炎小鼠中的作用

目的:研究IL-17 对病毒性心肌炎小鼠的作用。方法:随机挑选20只野生型BALB/ c 小鼠为对照组,20 只IL-17A-/ -小鼠为IL鄄17A-/ -组,20 只L-17A-/ -小鼠为IL-17 组。每只小鼠腹腔注射柯萨奇病毒B3(Coxsackie virus B3,CVB3)建立VMC 模型。收集小鼠外周血利用ELISA 法检测血清中IL鄄17 水平,利用流式细胞术检测血清中Th17 细胞水平。CVB3 处理3d 后,对照组和L鄄17A-/ -组腹腔注射100 滋g IgG 抗体,IL-17 组注射100 g IL-17mAb。分别于CVB3 处理第3、7、14 天收集小鼠心肌组织。将小鼠心肌切片并H&E 染色进行病理学检查。检测小鼠心肌组织中病毒滴度。利用酶联免疫吸附法检测心肌组织IL-17、IL-23、IL-6 和TNF 的含量。结果:成功构建病毒性心肌炎小鼠。对第14 天收集的组织进行分析发现, IL-17 组小鼠血清中IL-17 和Th17 水平均显著低于对照组和IL-17-/ - 组。对照组小鼠心肌组织损伤程度明显高于IL-17A-/ - 组和IL-17组,IL-17 小鼠心肌组织损伤程度高于IL-17A-/ -组。对照组病毒滴度高于IL-17A-/ -组和IL-17 组,且随着CVB3 处理时间增加而增加。在补充IL-17 抗体后IL-17 组病毒滴度高于IL-17A-/ -组。在IL-17-/ -组和IL-17 组的IL-17、IL-23、IL-6 和TNF 水平均显著低于对照组。在补充IL-17 抗体后IL-17 组IL-17、IL-23、IL-6 和TNF 水平均显著高于IL-17-/ -组(P<0.05)。结论:IL-17 是参与病毒性心肌炎的重要炎症因子,而IL-17 缺失可保护小鼠心肌免受病毒性心肌炎损伤。     

消化道恶性肿瘤伴癌性腹水患者腹腔化疗前后血清及腹水IL-6和sIL-6R水平变化的意义

目的：探讨腹腔化疗对癌性腹水患者血清及腹水IL-6及sIL-6R水平影响及其临床意义。方法：采用放免法测定病人腹腔化疗前、治疗后四周血清及腹水IL-6水平变化,用ELISA同时测定sIL-6R水平变化,并与正常对照组相对比。结果：消化道恶性肿瘤伴癌性腹水患者血清IL-6和sIL-6R水平较正常对照组明显升高,腹水IL-6和sIL-6R水平较血清IL-6和sIL-6R水平明显增高。腹腔化疗后血清IL-6和sIL-6R水平下降,腹水IL-6和sIL-6R水平变化与血清水平变化相平行。且血清及腹水IL-6及sIL-6R水平变化与腹腔化疗是否有效有密切关系。结论：监测癌性腹水患者血清及腹水IL-6及sIL-6R水平变化是判断及预测腹腔化疗是否有效的途径之一。     

慢性肾衰患者血清IL-18、IL-10、sIL-2R、TNF-α水平变化

目的：研究CRF患者血清IL-18、IL-10、TNF-α、sIL-2R的水平变化及临床意义。方法：分别采用RIA和ELISA法检测CRF患者血清IL-18、IL-10、TNF-α、sIL-2R含量，并与正常对照组比较分析。结果：CRF患者血清IL-18、IL-10、TNF-α、sIL-2R明显高于正常对照组（P〈0．01）。结论：CRF患者多种细胞因子水平升高，血清IL-18和TNF-α水平升高提示了CRF的发生发展过程，而IL-10和sIL-2R升高则对其肾脏功能有一定的保护作用。     

局麻和全麻对病人血清IL-6、IL-8和M-CSF水平影响的初步探讨

目的：探讨了局麻和全身麻醉对手术病人血清IL-6、IL-8和M-CSF水平的影响。方法：根据不同的麻醉方法将68例胃部手术病人分为硬膜外麻醉组（A组）和静吸复合全麻组（B组）,每组34例。在麻醉诱导前、手术切皮和手术开始后1h抽取静脉血3ml,分别测定血清IL-6、IL-8和M-CSF浓度。结果：A组血清IL-6、IL-8和M-CSF含量在切皮和术中1h与术前比较有显著性差异（P〈0.05）;B组血清IL-6、IL-8和M-CSF含量无显著性差异（P〉0.05）;在切皮和术中1h,B组IL-6、IL-8和M-CSF含量比A组含量低（P〈0.05）。结论：静吸复合麻醉能明显降低IL-6、IL-8和M-CSF浓度,有一定的临床实用价值。     

细胞因子及特异性抗体的检测在肾综合征出血热诊断中的意义

探讨检测血清细胞因子及肾综合征出血热(HFRS) 病毒特异性抗体IgM和IgG的含量在HFRS发病机制及诊断中的意义.选择24例HFRS患者及30例健康人血清标本,采用生物素-亲和素-酶免疫技术检测IL-2、IL-6和TNF-α,ELISA方法检测血清HFRS病毒特异性抗体IgM和IgG,并对其进行统计学分析. 结果显示, ELISA法检测HFRS患者抗HFRS病毒IgM和IgG的阳性率分别为75.00 % 和50.00 %,健康对照组的抗体阳性率为零;HFRS患者血清IL-2、IL-6、TNF-α的含量分别为10.88±2.31pg/mL、256.46±102.51pg/mL和45.63±5.32pg/mL,高于健康对照组0.59±0.24pg/mL(P＜0.01)、53.8±19.21 pg/mL(P＜0.01)和5.81±3.58 pg/mL(P＜0.01). 结论 :HFRS患者血清IL-2、IL-6和TNF-α及血清特异性抗体IgM和IgG的含量较健康人明显升高,检测这些指标对该病发病机理、诊断及预后评价有一定意义.     

成都地区病毒性心肌炎的病毒病因研究

对成都地区１１４例成人病毒性心肌炎和４０例健康人群（对照组）咽拭子和血清标本进行病毒分离和病毒中和抗体检测，结果，心肌炎组分离出柯萨奇（Ｃｏｘ）Ｂ病毒，流感病毒，腺病毒（Ａｄｖ，孤儿病毒（ＥＣＨＯ）及脊髓灰质炎（Ｐｏｌｉｏ）病毒共３２株，对照组未分离到病毒，血清标本检查结果，心肌炎组的５９例双份血清中，其抗体〉４倍升高者３９例（包括分离阳性其恢复期抗体〉４倍升高者１５例）；５５份单份血清中，其抗体     

Graves’眼病患者血清IL-2、sIL-2R和TGF-β测定的临床意义

目的：探讨Graves’眼病患者血清IL-2、sIL-2R和TGF-β水平的变化、病情进展和病因学的关系。方法：对照组30名和Graves眼病30例患者的血清TGF-β含量均采用放射免疫分析;血清IL-2、sIL-2R均采用酶联免疫吸附试验。结果：30例Graves’眼病患者血清IL-2治疗前水平非常显著低于对照组（P〈0.01）;经免疫抑制剂治疗6个月后水平较治疗前升高非常显著,与对照组比较已无显著性差异（P〉0.05）;sIL-2R含量治疗前非常显著的高于治疗后组和对照组（P〈0.01）;经用上述方案治疗后与对照组比较下降非常显著,但仍存在显著性差异（P〈0.05）;血清TGF-β浓度在治疗前非常显著地高于对照组（P〈0.01）;经治疗后显著下降,但与对照组比较差异仍非常显著（P〈0.01）。结论：Graves’眼病患者血清IL-2、sIL-2R和TGF-β三项血清指标的测定对于了解和认识其发病机理及预估病情有帮助。     

Serum levels of soluble IL-2 receptor, IL-4 and IgE-binding factors in childhood allergic diseases.

The serum levels of soluble IL-2 receptor (sIL-2R), IL-4 and IgE-binding factors were examined in children with allergic diseases, and compared with those in non-allergic controls of the same age and sex. The results showed age-related decreases in the serum levels of sIL-2R and IgE-binding factors, but not in that of IL-4 in both allergic and non-allergic individuals. Significant elevation of sIL-2R was observed in sera from children with atopic eczema or history of an anaphylactic reaction to food, as compared with that in non-allergic controls. The serum concentration of IL-4 was elevated in all allergic groups, including cases of atopic eczema, bronchial asthma and anaphylaxis to food, compared with non-allergic controls, and was correlated significantly with the serum level of IgE (r = 0.59). The IgE-binding factor levels in sera from patients aged 6-10 years with bronchial asthma, or patients aged 1-5 years with a history of food anaphylaxis were elevated as compared with those in non-allergic controls of same age. There was no significant correlation between the serum levels of IgE-binding factors and IgE. Since sIL-2R is released by activated T cells, the present study is in favour of T cell activation causing allergic skin disorders. The serum levels of IL-4 as well as IgE did not differ among allergic patients of different clinical categories. The role of IgE in atopic eczema and other allergic diseases is not clearly established; however, it seems likely that IL-4 is deeply involved in the increased production of IgE seen in allergic individuals. The possible involvement of IgE-binding factors in the age-related changes of clinical manifestations in childhood allergic diseases was also discussed.     

Evaluation of soluble IL-6 receptor concentration in serum and epithelial lining fluid from patients with interstitial lung diseases.

We measured soluble IL-6 receptor (sIL-6R) levels in serum and bronchoalveolar lavage fluids (BALF) from patients with interstitial pneumonia of unknown etiology (IP) (n = 17), sarcoidosis (n = 8) and normal control subjects (n = 10), to investigate its role in pulmonary diseases. Soluble IL-6R was determined by an ELISA. The volume of epithelial lining fluid (ELF) in BALF was estimated using an urea method. We found that levels of sIL-6R in serum, BALF, and ELF from patients with IP or sarcoidosis were significantly higher than those from normal subjects. Furthermore, levels of sIL-6R in BALF or ELF were significantly correlated with those of albumin, indicating that sIL-6R, together with albumin, may enter ELF as a result of the increased permeability caused by pulmonary inflammation. Thus most of the sIL-6R in ELF would be from serum, and relatively small amounts of it might be produced locally. However, sIL-6R levels in ELF, but neither serum nor BALF, were significantly correlated with levels of C-reactive protein in patients with IP. These results suggest that both systemic and local production of sIL-6R are increased, and raised sIL-6R is involved in the modulation of systemic and local inflammatory responses in patients with IP and sarcoidosis.     

High circulating levels of biologically inactive IL-6/SIL-6 receptor complexes in systemic juvenile idiopathic arthritis: evidence for serum factors interfering with the binding to gp130

We previously demonstrated that high levels of IL-6/sIL-6R complexes are present in sera of patients with systemic juvenile idiopathic arthritis (s-JIA) and that the amount of IL-6 estimated in the IL-6/sIL-6R complexes is markedly higher than that measured by the B9 assay. Here, we show that two additional bioassays, employing human myeloma XG-1 cells and human hepatoma Hep3B cells, detected serum IL-6 levels similar to those measured by the B9 assay and approximately 10-fold lower than the IL-6 levels estimated to be present in the IL-6/sIL-6R complex. Using an assay for the measurement of the amount of circulating IL-6 complexed with the sIL-6R and available for binding to gp130 (gp130 binding activity), we show that the IL-6/gp130 binding activity is similar to that detected by the bioassays and again significantly lower than that estimated to be present in the IL-6/sIL-6R complex. Addition of recombinant human IL-6 (rhIL-6) to sera of patients or controls results in a markedly lower increase in the gp130 binding activity in patients than in controls. Moreover, sera from s-JIA patients inhibited in a dose dependent manner the gp130 binding activity assay. These results show that sera from patients with s-JIA contain a factor, or factors, that inhibit(s) the binding of the IL-6/sIL-6R complex to gp130. This inhibitory activity does not appear to be due to soluble gp130, C-reactive protein or autoantibodies to IL-6.     

孟鲁司特对支气管哮喘患者血清IL-6、IL-8和IL-10水平的影响

目的:探讨孟鲁司特在支气管哮喘患者体内IL-6、IL-8和IL-10水平的影响。方法:应用放射免疫分析和酶联法对31例支气管哮喘患者应用孟鲁司特治疗前后血清IL-6、IL-8和IL-10水平的变化,并与35名正常健康人作比较。结果:支气管哮喘患者在治疗前血清IL-6、IL-8水平非常显著地高于正常人组(P<0.01),而IL-10水平显著地低于正常人组(P<0.01),经治疗2周后与正常人组比较仍有显著性差异(P<0.05)。结论:孟鲁司特对支气管哮喘患者血清IL-6、IL-8和IL-10有一定程度的调节作用,从而降低患者体内的炎症水平,促进病情缓解和好转。     

乙型病毒性肝炎患者血清IL-2、slL-2R、IL-13及PDGF测定的意义

目的：探讨乙型肝炎患者血清IL-2、sIL-2R、IL-13及PDGF水平的变化及测定的临床意义。方法：150例乙型肝炎患者分为3组（急性肝炎组20例、慢性肝炎组90例和重型肝炎组40例）;设健康人45名作为对照组。前2项血清标志物均采用放射免疫分析;后2项血清指标则采用酶联免疫吸附试验测定。将测定结果进行统计分析。结果：本文测定数值显示,血清IL-2水平急性肝炎患者组水平与对照组比较略有降低,但无统计学意义（P〉0.05）;慢性肝炎和重型肝炎2组患者该指标水平则均显著低于对照组（P均〈0.05）。sIL-2R水平显示急性、慢性及重型肝炎3组患者均非常显著地高于对照组（P均〈0.01）,且发现其递增规律与肝炎病情的严重程度呈明显的平行关系。IL-13水平测定结果也显示3组患者均显著高于对照组（P均〈0.05）。PDGF测定值显示,急性肝炎组水平显著高于对照组（P〈0.05）,慢性肝炎和重型肝炎2组水平则较对照组升高更为显著（P均〈0.01）。其水平的递增关系也与病情的严重程度相一致。结论：本文患者4项血清指标水平的变化与乙型肝炎的发病及病情进展有关;其测定有助于了解本病的发生机制和预后评估。     

婴幼儿感染者血清TNF、lL-6、lL-8联检的临床意义

目的:探讨了婴幼儿感染者血清TNF、IL-6、IL-8水平及其临床意义。方法:应用放免法对34例婴幼儿感染者进行了血清TNF、IL-6、IL-8检测,并以30名正常婴儿作比较。结果:婴幼儿感染者血清中TNF、IL-6、IL-8水平非常显著地高于正常人组(P<0.01),经治疗10d后,其水平显著下降,与正常人组比较无显著性差异(P>0.05)。结论:测定血清中TNF、IL-6、IL-8含量与患儿的危重程度发生、发展、预后有关。     

反复呼吸道感染儿sIL－2R和T细胞亚群的测定

本文采用双抗体夹心ＥＬＩＳＡ法分别测定了２１例反复呼吸道感染儿，３０例正常儿童，１０例新生儿脐血的血清可溶性白细胞介素２受体（ｓＩＬ＝２Ｒ）水平。结果患儿组ｓＩＬ－２Ｒ为７１６．６０±３０．１０Ｕ／ｍｌ；正常儿童组为３８４．４７±８８．０３Ｕ／ｍｌ（ｐ＜０．０１）；新生儿脐血为４４６．２０±５５．６８Ｕ／ｍｌ，与正常儿童比较Ｐ＞０．０５。同时采用间接免疫荧光技术测定了患儿Ｔ细胞亚群水平，结果ＣＤ８细胞数升高，ＣＤ３细胞和ＣＤ４细胞数、ＣＤ４／ＣＤ８比值下降，与正常儿童比较有显著性差别。提示反复呼吸道感染儿有细胞免疫功能降低及免疫调节紊乱。     

反复呼吸道感染儿sIL－2R和T细胞亚群的测定

本文采用双抗体夹心ＥＬＩＳＡ法分别测定了２１例反复呼吸道感染儿，３０例正常儿童，１０例新生儿脐血的血清可溶性白细胞介素２受体（ｓＩＬ＝２Ｒ）水平。结果患儿组ｓＩＬ－２Ｒ为７１６．６０±３０．１０Ｕ／ｍｌ；正常儿童组为３８４．４７±８８．０３Ｕ／ｍｌ（ｐ＜０．０１）；新生儿脐血为４４６．２０±５５．６８Ｕ／ｍｌ，与正常儿童比较Ｐ＞０．０５。同时采用间接免疫荧光技术测定了患儿Ｔ细胞亚群水平，结果ＣＤ８细胞数升高，ＣＤ３细胞和ＣＤ４细胞数、ＣＤ４／ＣＤ８比值下降，与正常儿童比较有显著性差别。提示反复呼吸道感染儿有细胞免疫功能降低及免疫调节紊乱。     

IL-6 and soluble IL-6 receptors (sIL-6R and sgp130) in human pleural effusions: massive IL-6 production independently of underlying diseases

IL-6, soluble IL-6 receptor (sIL-6R) and soluble gp130 (sgp130) levels were measured in sera and pleural effusions from 42 patients with metastatic carcinoma, non-Hodgkin's lymphoma, tuberculosis, cardiac failure and miscellaneous diseases. Pleural IL-6 levels measured by ELISA were very high in all patient groups (mean 34.8 ± 15.3 ng/ml) without significant difference according to diseases. IL-6 was shown to be biologically active in a proliferative assay. Serum IL-6 levels were low (0.049 ± 0.014 ng/ml) and did not correlate with pleural fluid levels. Pleural IL-6 levels correlated with the number of polymorphonuclear cells in pleural fluid (P< 0.03). Pleural sIL-6R levels (76 ± 8 ng/ml) were always lower than serum levels (196 ± 12 ng/ml; P< 0.0001) but correlated with them (P< 0.01). Pleural sIL-6R and albumin levels correlated (P< 0.01), suggesting a transudation of sIL-6R from the serum. Pleural sgp130 levels (10.9 ± 1.0 ng/ml) were lower than serum levels (24.6 ± 2.8 ng/ml; P< 0.002). After gel filtration of pleural fluid, the bulk of IL-6 (>90%) was recovered in a 15 000–30 000 fraction, corresponding to the expected mol. wt of free IL-6. These results suggest a production and a sequestration of IL-6 in the pleural cavity in all studied conditions.     

IL-2 regulation of soluble IL-2 receptor levels following thermal injury.

In the immunosuppressed burn patient serum levels of both IL-2 and a soluble form of IL-2 receptor alpha (sIL-2R alpha) are significantly elevated. Strikingly, the production of these markers by the in vitro activated patients' cells is decreased. This study examines the role of IL-2 in the decreased production of the sIL-2R alpha in vitro in patients with major burns (n = 18, 30 to greater than 70% total body surface area). Peripheral blood mononuclear cell (PBMC) cultures from patients with highly elevated serum sIL-2R alpha, and from healthy controls (n = 12) were activated with concanavalin A (Con A) at initiation. In patients' cultures mitogen-induced increments of sIL-2R alpha levels were significantly lower. There was a significant negative correlation (r = 0.64, P less than 0.001) between a high serum sIL-2R alpha level and a decreased lectin-induced sIL-2R alpha release in vitro. Low levels of sIL-2R alpha in patients' samples were not normalized by increasing the number of T lymphocytes. Also exogenous rIL-1 was without effect, whereas rIL-3 increased sIL-2R alpha release in some cultures. However, sIL-2R alpha levels were significantly increased in patients' cultures by (i) addition of exogenous IL-2; (ii) removal of adherent cells; (iii) addition of cyclooxygenase inhibitor, indomethacin; (iv) bypassing cell surface activation by the combination of the calcium ionophore A23187 and the phorbol ester 12-o-tetradecanoyl acetate. The cyclic AMP-elevating drug, forskolin, abrogated the ability of exogenous IL-2 to increase sIL-2R alpha production. Thus, in the burn patient, the reduced in vitro sIL-2R alpha release appears to relate to abnormalities in IL-2 production and action mediated through its functional surface receptor. Elevated levels of sIL-2R alpha in vivo may, therefore, reflect systemic activation of T lymphocytes in response to biologically active IL-2.