前列腺素E1对ARDS病人TNF-α IL-1β IL-6 IL-8的影响

目的 观察PGE1对急性呼吸窘迫综合征(RDS)病人细胞因子TNF-α、IL-1β、IL-6、IL-8的影响,探讨PGE1治疗ARDS的可能作用机制。方法 61例ARDS病人随机分为PGE1治疗组和对照组,应用放射免疫技术测定ARDS机械通气即刻、48h、5d时细胞因子TNF-α、IL-1β、IL-6、IL-8的水平。结果 PGE1治疗组在ARDS机械通气48h、5d时细胞因子TNF-α、IL-1β、IL-6、IL-8活性比对照组显著降低(P<0.01)。结论 PGE1可降低ARDS病程细胞因子活性。     

Association of IL-1Ra gene polymorphism, but no association of IL-1beta and IL-4 gene polymorphisms, with Kawasaki disease

The purpose of this study was to evaluate whether IL-1 beta (IL-1beta promoter and IL-1beta exon 5), IL-1 receptor antagonist (IL-1 Ra), and IL-4 (IL-4 promoter and IL-4 intron 3) gene polymorphisms act as markers of susceptibility to Kawasaki disease (KD), or of the severity of the disease. The study included 107 KD patients and 103 normal controls. Polymorphisms for cytokine genes were detected by polymerase chain reaction (PCR). Genotypes and allelic frequencies for cytokine gene polymorphisms in both groups were compared. No significant difference was observed in the genotypes and allelic frequencies of cytokines between patients with coronary aneurysm and without. In addition, there was no significant association in the genotype and allelic frequencies of IL-1 beta, IL-4, and IL-6 in patients with KD. The genotype I/II for IL1-Ra and the frequency of allele II for IL1-Ra are associated with a higher susceptibility to KD, and thus may be useful markers for predicting the development of KD.     

Divergence of IL-1, IL-18, and cell death in NLRP3 inflammasomopathies

The inflammasome is a cytoplasmic multiprotein complex that promotes proinflammatory cytokine maturation in response to host- and pathogen-derived signals. Missense mutations in cryopyrin (NLRP3) result in a hyperactive inflammasome that drives overproduction of the proinflammatory cytokines IL-1β and IL-18, leading to the cryopyrin-associated periodic syndromes (CAPS) disease spectrum. Mouse lines harboring CAPS-associated mutations in Nlrp3 have elevated levels of IL-1β and IL-18 and closely mimic human disease. To examine the role of inflammasome-driven IL-18 in murine CAPS, we bred Nlrp3 mutations onto an Il18r-null background. Deletion of Il18r resulted in partial phenotypic rescue that abolished skin and visceral disease in young mice and normalized serum cytokines to a greater extent than breeding to Il1r-null mice. Significant systemic inflammation developed in aging Nlrp3 mutant Il18r-null mice, indicating that IL-1 and IL-18 drive pathology at different stages of the disease process. Ongoing inflammation in double-cytokine knockout CAPS mice implicated a role for caspase-1–mediated pyroptosis and confirmed that CAPS is inflammasome dependent. Our results have important implications for patients with CAPS and residual disease, emphasizing the need to explore other NLRP3-mediated pathways and the potential for inflammasome-targeted therapy.     

系统性红斑狼疮患者血清可溶性细胞间粘附分子-1、L-选择素、细胞因子的变化及意义

目的探讨系统性红斑狼疮（SLE）患者血清可溶性细胞间粘附分子-1（sICAM-1）、L-选择素、白细胞介素（IL）-2、IL-6、IL-8和IL-10水平的变化及其致病意义。方法采自24例SLE患者的血清标本分别用酶联免疫吸附试验（ELISA）检测sICAM-1和L-选择素;用放射免疫检测法（RIA）检测IL-2、IL-6、IL-8和IL-10;另以20名健康志愿者作为对照。结果SLE患者血清sICAM-1、L-选择素、IL-6及IL-2/IL-10比值显著高于对照组（P〈0.05）,IL-2无明显变化,IL-8水平稍高于对照组,但差异无统计学意义（P〉0.05）。结论SLE患者sICAM-1、L-选择素和IL-6表达增加,而IL-10表达减少,提示免疫紊乱、促炎与抗炎细胞因子失平衡参与了SLE的发病过程。     

系统性红斑狼疮患者血清可溶性细胞间粘附分子-1、L-选择素、细胞因子的变化及意义

目的探讨系统性红斑狼疮(SLE)患者血清可溶性细胞间粘附分子-1(sICAM-1)、L-选择素、白细胞介素(IL)-2、IL-6、IL-8和IL-10水平的变化及其致病意义。方法采自24例SLE患者的血清标本分别用酶联免疫吸附试验(ELISA)检测sICAM-1和L-选择素;用放射免疫检测法(RIA)检测IL-2、IL-6、IL-8和IL-10;另以20名健康志愿者作为对照。结果SLE患者血清sICAM-1、L-选择素、IL-6及IL-2/IL-10比值显著高于对照组(P<0.05),IL-2无明显变化,IL-8水平稍高于对照组,但差异无统计学意义(P>0.05)。结论SLE患者sICAM-1、L-选择素和IL-6表达增加,而IL-10表达减少,提示免疫紊乱、促炎与抗炎细胞因子失平衡参与了SLE的发病过程。     

Impact of weight loss on circulating IL-1, IL-6, IL-8, TNF-alpha, VEGF-A, VEGF-C and midkine in gastroesophageal cancer patients

OBJECTIVE: Proinflammatory cytokines are involved in cancer-related weight loss, but the involvement of VEGF-A, VEGF-C, IL-8 and midkine in gastroesophageal cancer patients remains unknown. DESIGN AND METHODS: Serum IL-1, IL-6, IL-8, TNF-alpha, VEGF-A, VEGF-C, and midkine were evaluated in 96 cancer patients and 42 controls using ELISAs and were related to the occurrence of weight loss, patient's age, gender and BMI, cancer TNM status and blood cell counts. RESULTS: All cytokines were elevated in cancer patients with further up-regulation of IL-6, IL-8, midkine and VEGF-A in cachexia. Underweight, midkine and VEGF-A were found independent indicators of weight loss. Primary tumor seems to be a major source of pro-cachectic cytokines, yet neutrophils and platelets also contribute to cytokine elevation. CONCLUSIONS: IL-6 and IL-8, and probably midkine and VEGF-A, appear to participate in the development of cancer-related cachexia in gastroesophageal malignancies, although a detailed mechanism underlying cytokine involvement needs to be elucidated.     

Antibody to IL-1 or IL-15

There have recently been fewer publications written in Japanese describing inflammatory cytokines in rheumatoid arthritis (RA) other than tumor necrosis factor and interleukin (IL) -6. Interleukins such as IL-1 and IL-15 are thought to play an important role, at least in part, in pathogenesis of RA. In this review, the two interleukins above were mentioned from mainly RA point of view, respectively. Monoclonal antibody to each cytokine might be brought to the clinic in the future.     

脐血中GM-CSF、IL-2、IL-6和sICAM-1的表达水平及意义

目的探讨脐血中GM-CSF、IL-2、IL-6和sICMA-1的含量及其临床意义.方法采用ELISA法检测脐血和健康妇女血中GM-CSF、IL-2、IL-6和sICMA-1含量.结果脐血GM-CSF、IL-2和IL-6含量显著高于健康妇女(P<0.01),sICAM-1低于健康妇女(P<0.01).结论脐血中有丰富的造血细胞因子且未受病原体侵袭,临床应用有实用价值.     

多发性创伤后血清TNF-α、IL-1β、IL-6及IL-10变化的连续观察

目的 探讨创伤患者TNF－α、IL－1β、IL－6及IL－10血清浓度的变化及临床意义。方法 25例多发性创伤患者分别在受伤后第2、3、5、10及15天测定外周血清TNF－α、IL－1β、IL－6及IL－10的变化，并与正常对照组进行对比分析。血清TNF－α浓度采用放免法测定，IL－1β、IL－6、IL－10浓度采用酶联免疫吸附法测定。结果 TNF－α、IL－1β、IL－6及IL－10血清浓度在多发性创伤后均较正常对照显著增高，IL－1β及TNF－α于2周后恢复正常，而IL-6、IL-10增高持续至2周后。结论 TNF－α、IL－1β、IL－6及IL－10参与了多发性创伤病理生理过程，动态观察可能和病情程度有关。     

脐血中GM—CSF、IL—2、IL—6和sICAM—1的表达水平及意义

目的 探讨脐血中GM－CSF、IL－2、IL－6和sICAM-1的含量及其临床意义。方法 采用ELISA法检测脐血和健康妇女血中GM－CSF、IL－2、IL－6和sICAM-1含量。结果 脐血GM－CSF、IL－2和IL－6含量显著高于健康妇女（P＜0.01),sICAM-1低于健康妇女（P＜0.01)。结论 脐血中有丰富的造血细胞因子且未受病原体侵袭，临床应用有实用价值。     

Interleukin 1 (IL-1) gene expression, synthesis, and effect of specific IL-1 receptor blockade in rabbit immune complex colitis.

Interleukin 1 (IL-1) may be a key mediator of inflammation and tissue damage in inflammatory bowel disease (IBD). In rabbits with immune complex-induced colitis, IL-1 alpha and beta mRNA levels were detectable at 4 h, peaked at 12 but were absent at 96 h after the induction of colitis. Colonic IL-1 tissue levels were measured by specific radioimmunoassays. IL-1 alpha was significantly elevated at 4 h (9.4 +/- 1.5 ng/g colon), progressively increased at 48 h (31 +/- 5.8 ng/g) and then decreased by 96 h (11.5 +/- 3.4 ng/g). IL-1 beta levels were 2.0 +/- 0.5 ng/g colon at 4 h, 5.0 +/- 1.6 ng/g at 48 h and undetectable by 96 h. By comparison, colonic levels of PGE2 and LTB4 were unchanged during the first 12 h and did not become elevated until 24 h. IL-1 alpha levels were highly correlated with inflammation (r = 0.885, P less than 0.0001), edema (r = 0.789, P less than 0.0001) and necrosis (r = 0.752, P less than 0.0005). Treatment with a specific IL-1 receptor antagonist (IL-1 ra) before and during the first 33 h after the administration of immune complexes markedly reduced inflammatory cell infiltration index (from 3.2 +/- 0.4 to 1.4 +/- 0.3, P less than 0.02), edema (from 2.2 +/- 0.4 to 0.6 +/- 0.3, P less than 0.01) and necrosis (from 43 +/- 10% to 6.6 +/- 3.2%, P less than 0.03) compared to vehicle-matched colitis animals. These studies demonstrate that (a) IL-1 gene expression and synthesis occur early in the course of immune complex-induced colitis; (b) are significantly elevated for 12 h before the appearance of PGE2 and LTB4; (c) tissue levels of IL-1 correlate with the degree of tissue inflammation and; (d) specific blockade of IL-1 receptors reduces the inflammatory responses associated with experimental colitis.     

脑梗死患者血清白介素-6、白介素-8、肿瘤坏死因子-α及白介素-1β水平的研究

目的研究脑梗死患者急性期血清 IL -6、IL-8、TNF-α、IL -1β水平的变化 ,特别是 IL -6水平与脑梗死面积及神经功能缺损的关系。方法采用双抗体夹心 ELISA法检测 3 4例脑梗死急性期患者不同时间内血清 IL-6、IL -8、TNF-α、IL -1β水平 ,并随机抽取 10例健康人进行对照。结果脑梗死患者血清 IL -6水平在发病 6小时内明显升高 ,2 4～ 3 6小时达高峰 ,7天后基本降至正常 ,大面积梗死组IL-6水平明显高于小面积梗死组 ( 6小时内 ,P <0 .0 5 ;2 4～ 3 6小时 ,P <0 .0 5 ) ,且血清 IL -6水平与神经功能评分呈正相关( r=0 .87,P<0 .0 1) ,七叶皂甙钠治疗 3天后血清 IL-6水平下降明显 ( P<0 .0 1) ,脑梗死患者急性期血清 IL-8水平亦升高( P<0 .0 5 ) ,TNF-α、IL-1β水平则无明显变化。结论急性脑梗死患者血清 IL-6水平升高 ,而 IL-6升高的水平反映应激反应程度 ,与梗死面积及神经功能缺损程度有一定相关性。     

Tuning sensitivity to IL-4 and IL-13: differential expression of IL-4Ralpha, IL-13Ralpha1, and gammac regulates relative cytokine sensitivity

Interleukin (IL)-4 and -13 are related cytokines sharing functional receptors. IL-4 signals through the type I (IL-4Rα/common γ-chain [γc]) and the type II (IL-4Rα/-13Rα1) IL-4 receptors, whereas IL-13 utilizes only the type II receptor. In this study, we show that mouse bone marrow–derived macrophages and human and mouse monocytes showed a much greater sensitivity to IL-4 than to IL-13. Lack of functional γc made these cells poorly responsive to IL-4, while retaining full responsiveness to IL-13. In mouse peritoneal macrophages, IL-4 potency exceeds that of IL-13, but lack of γc had only a modest effect on IL-4 signaling. In contrast, IL-13 stimulated greater responses than IL-4 in fibroblasts. Using levels of receptor chain expression and known binding affinities, we modeled the assemblage of functional type I and II receptor complexes. The differential expression of IL-4Rα, IL-13Rα1, and γc accounted for the distinct IL-4–IL-13 sensitivities of the various cell types. These findings provide an explanation for IL-13's principal function as an “effector” cytokine and IL-4's principal role as an “immunoregulatory” cytokine.     

IL-1 beta, IL-2, IL-6 and TNF-alpha production by peripheral blood mononuclear cells from patients with Parkinson's disease.

The capacity of peripheral blood mononuclear cells (PBMC) from patients with treated Parkinson's disease (PD) to produce interleukin (IL) IL-1 beta IL-2, IL-6, tumor necrosis factor (TNF)-alpha and the proliferative response to mitogens, was compared with that from cells from healthy subjects. The production of IL-2 and the mitogen response were significantly lower in PD patients, whereas the secretion of IL-1 beta, IL-6 and TNF-alpha were significantly enhanced. To evaluate the role of levodopa in creating immunological alterations, PBMC of patients and controls were incubated with concentrations of the drug extrapolated from those used in clinical practice. Levodopa caused an inhibition of mitogen-induced proliferation, stimulation of IL-6 and TNF-alpha production, whereas the secretion of IL-1 beta and IL-2 was not affected. The results of the study provide a further support for the interrelationship between the central nervous and immune system. In addition, the data indicate that the immunological alterations found in PD may be partially attributed to levodopa administration.     

系统性红斑狼疮患者血清IL-17、IL-23、HMGB1表达水平及临床意义

目的探讨系统性红斑狼疮(Systemic lupus erythematosus,SLE)患者血清中白介素17(Interleukin-17,IL-17)、白介素23(Interleukin-23,IL-23)、高迁移率蛋白1(High mobility group box-1,HMGB1)的表达水平及临床意义。方法选取我院风湿免疫科收治的67例SLE患者为本研究观察组,同期选取22例体检健康志愿者为对照组,采用酶联免疫吸附试验(Enzyme linked immunosorbent assay,ELISA)检测所有受试者血清中IL-17、IL-23、HMGB1表达水平,分析三者表达与SLE临床指标之间的关系。结果观察组患者血清中IL-17、IL-23以及HMGB1水平均高于对照组,差异均显著,且具有统计学意义(P0.05),其中SLE活动组中IL-17、IL-23以及HMGB1水平均高于稳定组(P0.05),肾炎组HMGB1水平明显高于非肾炎组(P0.05),肾炎组IL-17、IL-23水平与非肾炎组比较无显著差异(P0.05);观察组IL-17水平与抗ds-DNA抗体水平、抗Sm抗体水平、补体C3、C4、IgM、IgG、CRP均无显著相关性(P0.05),与SLEDAI呈正相关(r=0.703,P0.05);IL-23水平与抗ds-DNA抗体水平、抗Sm抗体水平均无显著相关性(P0.05),与SLEDAI、IgM、IgG、CRP呈正相关(r=0.621、0.317、0.432,P0.05),与补体C3、C4呈负性相关(r=-0.456、-0.378,P0.05);HMGB1水平与抗Sm抗体水平、补体C4、CRP均无相关性,与SLEDAI、抗dsDNA抗体水平、IgM、IgG呈正相关(r=0.000,P0.05),与补体C3呈负性相关(r=0.000,P0.05)。结论血清IL-17、IL-23及HMGB1在SLE患者中显著高表达,且与疾病活动性密切相关,这些指标可能对揭示SLE发病机制或控制病情有一定的作用。