活动性肺结核患者血清sIL－2R与抗PPD抗体的相关性

应用ＥＬＩＳＡ检测了正常人和肺结核患者的血清可溶性白细胞介素２受体（ｓＩＬ－２Ｒ）和抗ＰＰＤ抗体水平。结果表明，活动性肺结核患者的血清ｓＩＬ－２Ｒ和抗ＰＰＤ抗体呈正相关（γ＝０．４３３，Ｐ＜０．００１），而且两者的水平明显高于正常对照组；抗ＰＰＤ抗体阳性的活动性肺结核患者血清中ｓＩＬ－２Ｒ浓度明显高于抗体阴性患者，提示血清ｓＩＬ－２Ｒ浓度测定可以反映肺结核患者细胞免疫功能状态。     

活动性肺结核患者血清sIL－2R与抗PPD抗体的相关性

应用ＥＬＩＳＡ检测了正常人和肺结核患者的血清可溶性白细胞介素２受体（ｓＩＬ－２Ｒ）和抗ＰＰＤ抗体水平。结果表明，活动性肺结核患者的血清ｓＩＬ－２Ｒ和抗ＰＰＤ抗体呈正相关（γ＝０．４３３，Ｐ＜０．００１），而且两者的水平明显高于正常对照组；抗ＰＰＤ抗体阳性的活动性肺结核患者血清中ｓＩＬ－２Ｒ浓度明显高于抗体阴性患者，提示血清ｓＩＬ－２Ｒ浓度测定可以反映肺结核患者细胞免疫功能状态。     

Soluble Interleukin-2 Receptor Levels and Immune Activation in Patients with Schistosomiasis and Carcinoma of the Urinary Bladder

Soluble interleukin-2 receptor (sIL-2R) level in serum is a marker of immune regulation and lymphocyte activation. Highly elevated levels of sIL-2R in serum were observed in patients of schistosomiasis with carcinoma of the bladder (SCB) and carcinoma of the bladder without schistosomiasis (CB) compared with patients with carcinoma of the prostate with or without schistosomiasis and normal healthy controls. Patients with SCB, who had an elevated percentage of cells expressing CD38+ activation antigen and CD71+ transferrin receptors in circulation, also had elevated levels of sIL-2R in serum. There were few interleukin-2 receptor (CD25+) positive cells in circulation in some patients with SCB. Despite this, the sIL-2R levels were extremely elevated. Our data suggest that in SCB, CD38+ and CD71+ cells may be the source of secretion of sIL-2R in serum. This relationship was confirmed by phenotypic characterizations of mononuclear cells and sIL-2R levels in individual patients. Measurements of sIL-2R levels in serum may provide a sensitive method of immune activation in patients with SCB.     

重症肌无力血清sIL-2R和AchR-ab水平变化的研究

本文对４０例健康成人和４０例不同临床类型的重症肌无力（ＭＧ）病人（全身型和眼肌型），进行了血清可溶性白细胞介素２受体（ｓＩＬ-２Ｒ）和乙酰胆碱受体抗体（ＡｃｈＲ-ａｂ）检测。结果发现全身型和眼肌型ＭＧ患者的ｓＩＬ-２Ｒ明显高于正常人（Ｐ＜０．００１），而全身型的ｓＩＬ-２Ｒ明显高于眼肌型（Ｐ＜０．０５）。ＡｃｈＲ-ａｂ阴性组的ｓＩＬ-２Ｒ明显高于ＡｃｈＲ-ａｂ阳性组（Ｐ＜０．０５）。ｓＩＬ-２Ｒ与ＡｃｈＲ-ａｂ之间经相关性分析，相关系数为-０．４２０８，Ｐ＜０．０５，呈明显负相关。     

T lymphocyte activation and restenosis after percutaneous transluminal coronary angioplasty.

We investigated the relation between the activation of T lymphocytes and the occurrence of restenosis after percutaneous transluminal coronary angioplasty (PTCA) in 10 stable angina patients. Recent studies have suggested that PTCA causes an inflammatory response, which may affect restenosis after angioplasty. Soluble interleukin-2 receptor (sIL-2R) is a useful marker to evaluate the activation of T lymphocytes. sIL-2R was measured before and 2 h after successful PTCA, and 3-month follow-up coronary angiography was done to observe restenosis. Four of 10 patients showed restenosis. The restenosis group of 4 patients had a higher level of sIL-2R after PTCA than the no-restenosis group of 6 patients (495 vs. 274 U/ml, p < 0.01). This study suggests that sIL-2R may offer prognostic information after elective PTCA and identify a subgroup of patients at high risk for clinical restenosis in a few months.     

Soluble IL-2 receptor and tumour necrosis factor-alpha in plasma of haemophilia patients infected with HIV.

We measured plasma concentrations of soluble receptors for IL-2 (sIL-2R) and tumour necrosis factor-alpha (TNF-alpha) in 149 haemophilia patients. Soluble IL-2R levels were elevated in 37% of 62 HIV-seronegative patients (mean 570 +/- 27 U/ml versus 361 +/- 17 U/ml in the control group, P less than 0.0001), in 78% of 68 HIV-seropositive patients (928 +/- 49 U/ml, P less than 0.0001), and in 95% of 19 AIDS/ARC patients (1578 +/- 199 U/ml, P less than 0.0001 compared with controls and with HIV-seronegative patients; P less than 0.005 compared with HIV-seropositive asymptomatic patients). A negative correlation was observed between sIL-2R, relative and absolute numbers of CD4+ cells (P less than 0.0001), and CD4/CD8 ratios (P less than 0.0001). There was also a negative correlation between sIL-2R in plasma and the cellular expression of IL-2R (P less than 0.001). We found a significant association of sIL-2R and plasma neopterin (P less than 0.0001). With progression of the disease from HIV-seronegative to seropositive without symptoms and to full manifestation of AIDS/ARC, sIL-2R plasma levels increased. The highest levels were found at the time of diagnosis of AIDS/ARC, but the levels decreased again during the following 18 months. Eight per cent of HIV-seronegative patients, 32% of HIV-seropositive patients, and 24% of patients with AIDS/ARC had increased plasma TNF-alpha. We conclude that sIL-2R and TNF-alpha plasma levels are elevated in HIV-infected haemophilia patients and that sIL-2R is a marker for disease progression from asymptomatic HIV-seropositive to AIDS/ARC.     

Soluble interleukin-6 receptor (sIL-6R) in cerebrospinal fluid of patients with inflammatory and non inflammatory neurological diseases

IL-6 acts on target cells via the ligand-binding protein interleukin-6 receptor (IL-6R) and the affinity-converting and signal-transducing glycoprotein 130 (gp130). Soluble interleukin-6 receptor (sIL-6R) has an agonistic role because the soluble complex (IL-6/sIL-6R) can activate cells that do not express IL-6R and an antagonistic role as it enhances the inhibitory activity of sgp130. Soluble forms of both receptors, sIL-6R and sgp130, regulate the action of IL-6. sIL-6R was measured by a sensitive enzyme-linked immunosorbent assay in paired sera and cerebrospinal fluid (CSF) from 46 patients with inflammatory neurological diseases (IND), 45 patients with relapsing-remitting multiple sclerosis (RR-MS), 13 patients with primary progressive multiple sclerosis (PP-MS), 17 patients with other non inflammatory neurological diseases (NIND) and 13 mentally healthy individuals--healthy controls (HC). Patients with RR-MS had CSF sIL-6R levels comparable to those from patients with IND, but higher than patients with NIND and HC. A positive correlation between the CSF/serum albumin (QAlb) and CSF sIL-6R levels was observed in IND but not in RR-MS patients indicating that CSF sIL-6R levels in IND patients could be influenced by serum sIL-6R and blood brain barrier (BBB) permeability properties. RR-MS patients had higher values of [CSF/serum sIL-6R:CSF/serum albumin] (sIL-6R index) than IND patients suggesting that in multiple sclerosis (MS), the increase in CSF sIL-6R could be due to intrathecal synthesis of sIL-6R. The finding of increased CSF sIL-6R concentrations (>979 pg/ml) with sIL-6R index (>4.66), in correlation with positive oligoclonal bands in RR-MS patients, suggests that values of sIL-6R index > 4.66 indicate intrathecal increase of sIL-6R and might be used as an indicator of neuroimmunoregulatory and inflammatory processes in the central nervous system (CNS).     

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.     

肾移植受者血清TNF-α、IL-6和sIL-2R水平变化及临床意义

目的:探讨肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)和可溶性白细胞介素-2受体(sIL-2R)在肾移植术后急性排斥反应中的变化。方法:采用固相酶标记化学发光免疫分析技术动态监测36例患者肾移植前后血清TNF-α、IL-6和sIL-2R水平,并结合临床资料作全面分析。结果:肾移植受者术后第1天血清TNF-α、IL-6和sIL-2R均明显升高,其中移植稳定组血清IL-6和sIL-2R第1天出现峰值后开始下降,而TNF-α则在术后5天达峰值后开始下降,至第10天均接近术前水平。急性排斥组血清TNF-α、IL-6和sIL-2R水平与肾功能稳定组比较,差异有显著性(P<0.05),抗排斥治疗有效后迅速下降。而环孢素A中毒组与稳定组比较,差异无显著性(P<0.05)。结论:肾移植术后受者血清TNF-α、IL-6和sIL-2R水平的检测,可在一定程度上反映肾移植受者的免疫反应状态,并为急性排斥反应的监测和诊断提供客观依据。     

Soluble interleukin-2 receptor and disease activity in Crohn's disease.

An ELISA was used to measure concentrations of soluble interleukin-2 receptor (sIL-2R) alpha chain in the sera of patients with Crohn's disease. In a group of 56 patients, serum concentrations of sIL-2R were significantly raised in patients with active disease compared with patients with inactive disease and age-matched control populations. There was a significant correlation between serum sIL-2R concentration and disease activity as assessed by the Harvey-Bradshaw index (r = +0.60; P less than 0.001) and laboratory measurements of disease activity including C-reactive protein (r = +0.79; P less than 0.001), ESR (r = +0.64; P less than 0.001) and platelet count (r = +0.533; P less than 0.001). We also found a negative correlation between sIL-2R levels and serum albumin (r = -0.66; P less than 0.001). In longitudinal studies, changes in the concentration of serum sIL-2R reflected the changes in disease activity. Soluble IL-2R, therefore, offers a new measure of disease activity in Crohn's disease with a potential advantage over other laboratory parameters currently available in that it may reflect more accurately the underlying immunopathogenic process.     

肝硬化患者血清sIL-2R和T淋巴细胞亚群水平的探讨

目的：探讨了肝硬化患者血清可溶性白细胞介素-2（sIL-2R）和T淋巴细胞亚群的水平及意义。方法：应用ELISA和单克隆抗体法对54例肝硬化患者进行了血清sIL-2R和T淋巴细胞亚群的测定，并与30名正常健康人作比较。结果：肝硬化患者血清sIL-2R水平非常显著地高于正常人组（P〈0．01），经3个月的治疗后血清sIL-2R水平与正常人比较仍有差异（P〈0．05），且sIL-2R水平和T淋巴细胞亚群中的CD4／CD8细胞比值密切相关。结论：检测肝硬化患者血清sIL-2R和T淋巴细胞亚群水平可作为患者病情、预后判断的重要检测指标。     

大隐静脉曲张光凝治疗后血清IL-2和sIL-2R的测定

目的 :测定大隐静脉曲张血管内光凝治疗前后血清中白细胞介素 - 2 (sIL - 2R)及其可溶性受体(sIL - 2R)的变化。方法 :5 0例大隐静脉曲张患者根据症状分为轻、重两组 ,取静脉血液 ,分别采用放射免疫分析和双抗体夹心间接ELISA法检测血清中IL - 2和sIL - 2R水平。另外取 30例正常成人血清作为对照。结果 :大隐静脉曲张患者轻症组患者血清中IL - 2和sIL - 2R较正常水平没有明显改变 ;随着病情的加重 ,IL - 2水平明显降低 ,sIL - 2R水平明显升高。治疗后两组IL - 2先下降 ,后逐渐升高 ;sIL - 2R水平先升高 ,后下降。轻症组IL - 2和sIL - 2R稳定水平接近术前 ;而重症组IL - 2稳定后水平高于治疗前 ,sIL - 2R稳定水平低于治疗前水平。结论 :IL - 2和sIL - 2R水平测定可了解静脉曲张患者免疫功能状态 ,判定治疗后病情恢复情况。     

Soluble interleukin-2 receptor in sera of patients with Graves' disease.

Activation of T lymphocytes has been found to be associated with an increase in soluble interleukin-2 receptor (sIL-2R) levels. The aim of this study was to investigate serum levels of sIL-2R in 20 untreated patients with Graves' disease and to relate these levels to disease activity and to TSH-receptor, anti-thyroglobulin, anti-microsomal and anti-eye muscle antibodies. sIL-2R levels were significantly increased in newly diagnosed Graves' patients compared with controls (667 +/- 270 vs 205 +/- 45 U/ml) (P less than 0.001). The sIL-2R levels were higher in patients with active infiltrative ophthalmology than in those without eye symptoms (810 +/- 313 vs 525 +/- 180 U/ml). All patients were treated with methimazole for at least 12 months. sIL-2R levels were normalized by methimazole treatment in the majority of patients without ophthalmopathy but not in those with ophthalmopathy. In five patients sIL-2R serum levels were studied after interruption of thyrostatic therapy. An increase was observed in three patients and hyperthyroidism subsequently relapsed in two of these. Furthermore, a correlation was found between soluble interleukin-2 receptor levels and TSH-receptor antibodies but not with other immune parameters examined. Serum sIL-2R represents a useful marker of immunological activity in Graves' disease.     

肺结核患者血清可溶性白细胞介素－2受体检测的临床意义

应用夹心法ＥＬＩＳＡ测定肺部疾病患者血清可溶性白细胞介素２－受体（ｓＩＬ－２Ｒ），结果表明，进展期肺结核及急性肺炎患者血清ｓＩＬ－２Ｒ较正常对照组的明显升高，进展期肺结核及好转期肺结核患者血清ｓＩＬ－２Ｒ，较稳定期肺结核患者的增高（Ｐ＜０．０１）。进展期肺结核患者血清ｓＩＬ－２Ｒ的高低与肺部病灶大小有关。经抗结核化疗后，进展期肺结核患者血清ｓＩＬ－２Ｒ降低或无改变。与Ｘ线胸片和／或痰菌改变一致，提示测定肺结核患者血清ｓＩＬ－２Ｒ，有助于对进展期肺结核患者疾病活动性的判断。     

胸腺扩大切除治疗重症肌无力围术期血清IL-17、IL-18、IL-27水平分析

目的探讨胸腺异常合并重症肌无力（MG）患者行胸腺扩大切除术后外周血血清IL—17、IL-18、IL-27等细胞因子的变化情况及其意义。方法选取16例未经免疫抑制治疗的MG患者行胸腔镜下胸腺扩大切除术,采用双抗体夹心ELISA法检测术前及术后第7El外周血血清IL-17、IL．18、IL．27水平,以15例健康献血者的血清IL-17、IL-18、IL-27水平作为正常对照。结果胸腺切除术后MG患者外周血IL-17、IL-18、IL-27水平普遍降低,外周血IL-17、IL-18、IL-27水平在胸腺瘤和胸腺增生两种病理类型中无明显差异。结论手术切除胸腺可降低MG患者外周血IL-17、IL-18、IL-27水平。     

Serum interleukin-2-receptor in coeliac disease: response to treatment and gluten challenge.

Concentrations of the soluble interleukin-2 receptor (sIL-2R) in the serum of 33 patients with coeliac disease were measured by ELISA. The levels of sIL-2R were significantly raised in 15 patients with untreated coeliac disease compared with treated patients and age- and sex-matched symptomatic and non-symptomatic control groups. Longitudinal studies in individual coeliac patients showed that serum sIL-2R fell following commencement of a gluten-free diet. Gluten challenge of 16 treated coeliac patients for 1 week resulted in a significant increase in serum sIL-2R, which returned to prechallenge levels within 4 weeks of recommencement of a gluten-free diet. We suggest that serum sIL-2R levels in patients with coeliac disease reflect specific immunological activation in response to gluten ingestion. Measurement of serum sIL-2R may therefore be useful in the assessment of response to treatment in patients with coeliac disease.     

Altered levels of the soluble IL-1, IL-4 and TNF receptors, as well as the IL-1 receptor antagonist, in intermittent allergic rhinitis

BACKGROUND: The effects of cytokines are modulated by soluble cytokine receptors (SCR) and receptor antagonists. Therefore, allergic disease may depend on altered proportions between cytokines, their SCR and receptor antagonists, rather than absolute changes in cytokine levels. Little is known about SCR in intermittent allergic rhinitis (IAR). OBJECTIVE: To examine the concentrations of SCR, i.e. sIL-1R2, sIL-4R, sIL-6R and sTNFR1, as well as the interleukin-1 receptor antagonist (IL-1Ra) in nasal fluids from allergen-challenged patients with IAR and healthy controls. METHODS: 30 patients with birch- or grass-pollen-induced IAR and 30 healthy controls were studied. In the patients nasal fluids were obtained before as well as 1 and 6 h after allergen provocation. RESULTS: Both symptom scores and rhinoscopic signs of rhinitis increased in the patients after allergen challenge. Comparisons between patients and controls showed that sIL-4R was lower in patients before and 1 and 6 h after provocation. IL-1Ra was lower before and 1 h after provocation. In addition, lower concentrations of sTNFR1 were found in patients after 1 h, while sIL-1R2 concentrations were higher after 1 h. Comparisons of patients before and after challenge showed that IL-1Ra and sTNFR1 decreased after 1 h, while sIL-1R2 increased. No significant differences were found compared to 6 h. sIL-6R did not significantly differ between the study groups. CONCLUSIONS: After allergen challenge, significant changes in the nasal fluid levels of IL-1Ra, sIL-1R2 and sTNFR1 were found. By contrast, sIL-4R remained at lower levels than in controls both before and after challenge. Since sIL-4R modulates IgE synthesis, this may play a role in the pathogenesis of IAR.     

Monitoring of disease activity by measurement of inflammatory markers in atopic dermatitis in childhood

Serum levels of soluble interleukin-2 receptor (sIL-2R), intercellular adhesion molecule-1 (ICAM-1), endothelial leukocyte adhesion molecule (ELAM-1), and eosinophil cationic protein (ECP) were measured in 20 patients with atopic dermatitis before and after 4 days'treatment with prednisolone p.o. as well as in 16 healthy, nonatopic controls. Before steroid treatment, patients with atopic dermatitis demonstrated significantly higher serum levels of sIL-2R, ICAM-1, and ECP than healthy controls (P<0.001), whereas ELAM-1 levels were not different between the groups. After 4 days of steroid treatment, clinical improvement was associated with a decrease of sIL-2R (P<0.003), ICAM-1 (P<0.004), and ECP serum levels (P<0.003), but ELAM-1 levels remained unchanged. Both serum ECP and slL-2R levels were significantly correlated with disease severity before as well as after steroid treatment. Changes of sIL-2R concentrations were strongly related to the changes of ECP levels. In addition, changes of serum sIL-2R and ECP levels in percentage were correlated with clinical improvement. These results indicate that the determination of sIL-2R and ECP serum levels may be useful in monitoring disease activity in atopic dermatitis in childhood, especially in treatment trials.     

Serum interleukin-2 receptor responses to immunization

Serum interleukin-2 receptor (sIL-2R) levels have been used to assess immune activation in inflammatory and infectious illnesses, although the cellular origin of these receptors and the dynamics of their production are not well defined. To investigate the relationship between sIL-2R levels and the degree of immune activation in antigen-specific responses, sIL-2R were measured in healthy individuals after both primary and secondary immunization with keyhole limpet hemocyanin (KLH). Despite induction of strong antibody responses, KLH immunization did not result in consistent elevations of sIL-2R levels, with only one of six subjects developing a substantial (twofold) increase in sIL-2R levels. The absence of sIL-2R elevation after a discrete antigenic stimulus suggests that inflammatory illnesses in which elevated sIL-2R levels have been noted involve more extensive stimulation of immune cells, either in number or in degree, than that present after simple immunization in healthy individuals.     

Increased and highly stable levels of functional soluble interleukin-6 receptor in sera of patients with monoclonal gammopathy

Soluble human interleukin-6 receptor (sIL-6R) was measured in the serum of 30 healthy individuals, 32 individuals with monoclonal gammopathy of undetermined significance (MGUS), 20 patients with early multiple myeloma (MM) and 54 patients with overt MM. The serum activity recognized by an immunoradiometric assay was determined to be sIL-6R, because of its binding capacity to IL-6 and its molecular mass of 55 kDa. All sera of healthy individuals contained sIL-6R (mean value: 89 ng/ml, range 17-300 ng/ml). Serum sIL-6R levels were increased by 51% in patients with MGUS (mean value: 135 ng/ml, p<0.005), by 44% in patients with early myeloma (mean value: 128 ng/ml, p<0.001) and by 116 % in patients with overt MM (mean value: 193 ng/ml, p<0.001). In patients with MM, a complete lack of correlation (p>0.7) was found between serum sIL-6R levels and other previously recognized prognostic factors in this disease, particularly serum IL-6 levels and those factors related to tumor cell mass. The independence of serum sIL-6R levels on tumor cell mass was directly demonstrated by studying four patients with MM treated with autologous bone marrow transplantation for periods of between 320 and 760 days. These levels were found to be remarkably stable and constant, independent of whether patients relapsed or achieved complete remission. Finally, physiological concentrations of sIL-6R were found to increase by tenfold the sensitivity of human myeloma cell lines to IL-6. These observations suggest a high control of the sIL-6R level in vivo, and, possibly, an important functional role of this circulating protein in patients with monoclonal gammopathies.