本草九代对慢性迁延性肝炎患者血清可溶性白细胞介素2受体水平的调节作用

用ELISA方法检测了29名慢性迁延性肝炎患者和18名健康献血员血清可溶性白细胞介素2受体(sIL-2R)水平,同时进行了血清IL-2与sIL-2R的相关分析。结果发现,正常人sIL-R为147±72.1u/ml,而慢性迁延性肝炎病人sIL-2R显著升高(210.5±84).GWe治疗3个月后sIL-2水平显著下降(185.8±79);同时发现IL-2水平与sIL-2R 有一定相关性。上述结果提示GWe具有调节机体IL-2功能的独特作用。     

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。     

重型乙型肝炎患者外周血中IL-2系统的初步研究

以放射免疫分析法、微量细胞培养法检测31例重型乙型肝炎患者血清和用PHA-P、rIL-2刺激外周血PBMC的培养上清中IL-2、sIL-2R含量,以间接免疫荧光法检测培养后PBMC中Tac~+细胞数,结果显示:重型乙型肝炎患者血清、培养上清中sIL-2R含量和Tac~+细胞数显著高于慢性活动型肝炎、急性黄疸型肝炎及献血员对照组,而血清、上清中IL-2含量与急性肝炎接近,但显著高于慢性活动性肝炎患者(P<0.01)。提示:重型乙型肝炎患者IL-2R表达增强,PBMC处于较高的免疫活化状态,其IL-2系统的生物学活性有可能高于各对照组。     

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。     

血浆sIL-2R对急性期川崎病调节性T 细胞的影响

目的探讨sIL-2R血浓度对急性期川崎病（ KD）患儿调节性T细胞（ Treg）的影响。方法急性期KD患儿33例,正常同龄对照儿童14例。流式细胞术检测外周血CD4＋CD25＋Foxp3＋Treg细胞的比例和CD4＋CD25＋T细胞磷酸化STAT5（pSTAT5）蛋白平均荧光强度（MFI）;流式微球阵列术（CBA）检测血浆sIL-2R、IL-2、IL-7、IL-15的浓度;荧光定量PCR（real-time PCR）检测CD4＋CD25＋T细胞Foxp3、GITR、CTLA-4、IL-2Rα、IL-2Rβ、IL-2Rγ和CD 4＋CD25-T 细胞 IL-17A、RoR-γt 等基因mRNA表达。结果（1）急性期KD患儿CD4＋CD25＋Foxp3＋Treg细胞比例及相关分子Foxp3、GITR、CTLA-4 mRNA表达明显低于同龄对照组（P＜0．05）,Th17细胞相关因子IL-17A、ROR-γt mRNA表达明显增高（P＜0．05）,IVIG治疗后呈不同程度的恢复（P＜0．05）。（2）急性期KD患儿CD4＋CD25＋T细胞pSTAT5蛋白水平显著下调（P＜0．05）,IVIG治疗后明显上调（P＜0．05）。（3）急性期KD患儿血浆sIL-2R浓度显著增高（P＜0．05）,IVIG治疗后下降（P＜0．05）;其中KD合并冠脉损伤组（KD-CAL＋）明显高于无冠脉损伤组（KD-CAL-）（P＜0．05）;IL-2、IL-7、IL1-5浓度无明显改变（P＞0．05）。（4）急性期KD患儿CD4＋CD25＋T细胞IL-2Rα、IL-2Rβ基因mRNA表达明显低于同龄对照组（P＜0．05）,IVIG治疗后呈不同程度的升高（ P＜0．05）;IL-2Rγ基因mRNA表达无明显改变;sIL-2R血浓度与IL-2RβmRNA、pSTAT5及Foxp3 mRNA表达呈负相关（ P＜0．05）;pSTAT5与Foxp3 mRNA表达呈正相关（ P＜0．05）。结论血浆sIL-2R明显增高可致IL-2/STAT5信号途径传导异常,这可能是导致急性期KD Treg细胞下调的因素之一。     

重症肌无力患者胸腺切除术后sIL-2R水平的跟踪观察

重症肌无力(MG)是以神经肌肉传导改变为特征的一种典型的获得性自身免疫性疾病.85%以上的MG患者血清中有不同水平的抗乙酰胆碱受体(AchR)的自身抗体,但其滴度与疾病的严重程度无严格的相关性.最近证明MG患者的胸腺及外周血中的T细胞对重组白细胞介素2(rIL-2)的反应性增强,可不通过预先刺激而被rIL=2激活,提示MG患者可能有IL-2R调控和/或表达的异常可溶性白细胞介素2受体(sIL-2R).的血清水平是细胞激活的早期标志,在细胞sIL-2R生长期间可能还具有免疫调节功能.通过测定sIL-2R在胸腺切除术前和术后的血清水平,研究MG患者免疫系统的活化状态及估计在随访中sIL-2R是否可作为疾病严重程度的标志.     

全身性红斑狼疮患者T淋巴细胞亚群和sIL-2R变化的观察

观察全身性红斑狼疮（SLE）患者的TI林巴细胞亚群,NK细胞及可溶性白介素2受体（sIL-2R)的变化。以了解患者细胞免疫门节紊乱的发病机制。采用流式细胞术对60例活动性SLE患者和30名对照组进行CD3 ,CD4 ,CD8 ,NK,CD4 /CD45Ra等细胞表面标志的检测;采用ELISA法检测,sIL-2R,结果表明,SLE患者外周血中CD8＋细胞增加,而细胞CD4＋,CD4＋／CD45Ra 细胞和NK细胞均减少,CD3＋细胞无明显变化,sIL-2R水平明显增高,本文的结果提示,活动性SLE患者发病与细胞免疫调节紊乱有关。     

妊娠17～37周胎儿可溶性白介素2受体和NK细胞含量的变化

目的：探讨妊娠17～37周正常和宫内感染时胎儿外周血可溶性白介素2受体（Soluble interleuldn-2 receptor，sIL-2R）和自然杀伤细胞（Natural killer，NK）含量的变化。方法：超声引导下行脐带穿刺术，收集129例胎儿外周血，包括97例正常对照组胎儿血，32例宫内感染组（单纯疱疹病毒感染、弓形虫感染、风疹病毒感染）胎儿血，采用双色免疫荧光标记流式细胞仪技术测定胎JLPF周血NK细胞百分率，双抗体夹心酶联免疫吸附试验测定胎JLPF周血中sIL-2R的含量，分析生理状态下胎儿外周血NK细胞、sIL-2R的状况和宫内感染时NK细胞和sIL-2R含量的变化。结果：妊娠17—37周胎儿外周血NK细胞、sIL-2R含量不随孕周改变，r（NK）=-0．03，P〉0．05；r（sIL-2R）=0．167，P〉0．05，宫内感染时NK细胞含量减少，sIL-2R含量增多，与正常对照组相比差异有显著意义；t（NK）=4．29，P〈0．01；t（sIL-2R）=-5．833，P〈0．01。结论：妊娠17—37周胎儿外周血有一定量的NK细胞和sIL-2R存在，但机体免疫功能仍不完善，宫内感染时机体容易出现免疫抑制状态。     

慢性乙型肝炎患者血清sIL-2R与肝硬化的关系

目的:探讨肝硬化病人血清sIL-2R与ⅣC、LN、HA的变化,探讨慢性乙型肝炎患者sIL-2R水平与肝脏病理炎症和纤维化程度的关系。方法:100例按炎症和纤维化程度分组,32例对照,检测血中sIL-2R、ⅣC、LN和HA的含量,采用放射免疫分析。结果:sIL-2R、ⅣC、LN和HA的水平明显高于对照组(P<0.05～0.01);并随肝纤维化的进展而增高;sIL-2R水平随着肝组织炎症程度加重而加大;sIL-2R与ALT、AST、γ-GT、ALP呈显著正相关(r=0.5681;r=0.5784;r=0.5711;r=0.5841;P均<0.05)。结论:sIL-2R的变化可作为肝纤维化或肝硬化诊断的参考指标之一。     

抑郁症患者IL-2及sIL-2R的检测及临床意义

目的　探讨白介素 -2 ( IL-2 )及可溶性白介素 -2受体 ( s IL-2 R)在抑郁症发病中的作用及临床意义。方法　用酶联免疫吸附法检测 30例抑郁症患者和 30例正常人血清 IL-2及 s IL-2 R水平 ,并比较二者的差异。结果　抑郁症患者 IL-2及 s IL-2 R分别为 95 1 .2± 1 1 0 .5 ngl/L、( 389.6± 2 1 1 .1 ) U/ml,高于对照组的 384 .1± 72 .5 ng/L、2 83.6± 1 4 6 .7U/ml,二者比较差异有显著性 ( P<0 .0 1 )。结论　抑郁症患者 IL-2及 s IL-2 R水平增高。     

Early IL-2/sIL-2R surge following surgery leads to temporary immune refractoriness.

High serum level of immunoreactive but not biologically active IL-2 was detected 1 day after surgery in patients undergoing major operation (abdominal, open-heart), in proportion to the tissue injury caused by surgical trauma. IL-2 values were highest in those patients who underwent open-heart surgery and received blood transfusions. In all patients they declined in the third and fourth post-operative days. Elevated serum levels of soluble IL-2 receptors (sIL-2R) were already present 1 day after operation, and peaked in the third and fifth post-operative days after mitogen triggering. Blood lymphocytes derived from operated patients secreted reduced amounts of both IL-2 and sIL-2R compared with control lymphocytes. The extent and duration of this reduction were also proportional to the tissue trauma and were affected by blood transfusions. Based on these data we suggest that early post-operative systemic immunological activation (appearance of IL-2 in the serum) is followed by elevation of sIL-2R, which then interferes with IL-2-dependent immunity. Blood lymphocytes are probably not involved in the post-operative immunological activation. The trigger for and the site of IL-2/sIL-2R synthesis are not yet clear.     

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。     

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.     

Plasma soluble interleukin-2 receptor (sIL-2R) levels in patients with acute leukemia

The plasma soluble interleukin-2 receptor (sIL-2R) level was higher in 137 patients with acute leukemia (1,489 +/- 1,798 U/ml, including 98 cases of acute myeloid leukemia (AML), 1,063 +/- 1,414 U/ml, and 39 cases of acute lymphoblastic leukemia (ALL), 2,561 +/- 2,194 U/ml), compared to 49 normal control subjects, 421 +/- 151 U/ml). The ALL patients showed elevated plasma sIL-2R levels more frequently than the AML patients (92.3% vs 44.9%). No patient with either hypoplastic AML or AML with multilineage dysplasia and only 1 of 13 patients with acute promyelocytic leukemia (APL) had an elevated plasma sIL-2R level. All the My+ ALL patients (15 cases) showed elevated plasma sIL-2R levels. Plasma sIL-2R levels were significantly lower after chemotherapy in the ALL patients, but were not significantly lower in the AML patients. IL-2R was expressed on the leukemic cells in 36 (53.7%) of 67 AML and in 9 (21.4%) of 42 ALL cases. None of the AML M3, M4, M5, M6, or M7 subgroups showed IL-2R expression. The My+ ALL patients (42.9%, 6/14) showed IL-2R expression more frequently than the other ALL subgroups (10.7%, 3/28) (p = 0.025). The plasma sIL-2R level was correlated with the proportion of leukemic cells expressing IL-2R in acute leukemia. However, there were many cases, particularly ALL cases, who had elevated plasma sIL-2R levels without IL-2R expression on their leukemic cells. These results suggest that the plasma sIL-2R level is a valuable marker for monitoring ALL after chemotherapy, particularly in My+ ALL cases, and that the T cell immune reaction to leukemia appears to be much higher in ALL patients than in AML patients.     

Soluble plasma IL-2 receptors and malaria.

Plasma levels of soluble IL-2 receptor (sIL-2R) were measured by immunoassay in 180 individuals, aged 1-70 years, living in a malaria-endemic community in West Africa. sIL-2R levels were compared with age, malaria parasitaemia, malaria-associated morbidity and cellular immune responses to Plasmodium falciparum antigens. Plasma levels of sIL-2R were independently associated with both age and patent malaria parasitaemia. No significant association was observed between IL-2R levels and concurrent malaria morbidity (i.e. fever associated with malaria), but the number of individuals with clinical malaria at the time of sampling was small. Although there was no association between plasma sIL-2R levels and in vitro proliferative responses of peripheral blood mononuclear cells (PBMC) to a number of defined malaria antigens, we did find a significant negative association between sIL-2R and in vitro proliferation of unstimulated PBMC. High levels of sIL-2R (up to 5500 U/ml) were detected in the plasma of malaria-infected individuals; this is indicative of a vigorous cellular immune response to malaria antigens in vivo and does not support the notion that malaria infections are generally immunosuppressive. Indeed, we found that, at the low levels of parasitaemia present in study subjects, there was no significant difference in the mean proliferative response to malaria antigens in infected subjects when compared with uninfected subjects.     

The correlation between interleukin 2 and soluble interleukin 2 receptors to oestradiol, progesterone and testosterone levels in periovulatory follicles of in-vitro fertilization patients.

The present study was performed to evaluate the correlation between follicular fluid levels of interleukin 2 (IL-2) and IL-2 soluble receptor (sIL-2R), oestradiol, progesterone and testosterone levels, oocyte fertilization, embryo quality and pregnancy rates. Twenty-eight patients with a pure tubal factor and undergoing in-vitro fertilization and embryo transfer were randomly chosen and treated with gonadotrophin releasing hormone agonist (GnRHa) in the midluteal phase (long protocol) coupled with follicular phase administration of human menopausal gonadotrophin. Transvaginal follicular aspiration was performed 36 h after human chorionic gonadotrophin administration, followed 48 h later by embryo transfer. One hundred and twenty-three follicular fluids were sampled. The mean follicular fluid levels (+/- SD) were 2.30 +/- 0.80 fmol for IL-2, 458.2 +/- 236.0 units/ml for sIL-2R, 28.5 +/- 58.1 ng/ml for oestradiol, 2360.5 +/- 2846 ng/ml for progesterone and 7.22 +/- 7.08 ng/ml for testosterone. There was a significant (P less than 0.01) correlation between IL-2 and testosterone levels. No correlation was found between the lymphokines and serum oestradiol, follicular fluid progesterone, oocyte fertilization, embryo quality and pregnancy. It may be concluded that significant concentrations of IL-2 and sIL-2R exist in follicular fluid. Wide variations in follicular IL-2 and sIL-2R concentrations of different follicles were found in the same patients.     

普乐可复对难治性肾病综合征患者血清IL-2、sIL-2R的影响及其临床意义

目的:研究普乐可复(FK506)对难治性肾病综合征患者血清IL-2、sIL-2R的影响及其临床意义。方法:应用酶联免疫吸附法检测难治性肾病综合征患者经普乐可复治疗前后血清IL-2、sIL-2R水平变化,并监测患者24小时尿蛋白、血浆白蛋白、血脂的变化。结果:难治性肾病综合征患者经普乐可复治疗前血清IL-2、sIL-2R水平均显著高于正常对照组(P<0.05)。治疗后血清IL-2、sIL-2R水平较治疗前明显下降(P<0.05)。治疗前24小时尿蛋白水平显著高于正常对照组(P<0.01),血浆白蛋白显著低于正常对照组(P<0.01),血脂水平显著高于正常对照组(P<0.01);与治疗前比较,治疗后24小时尿蛋白水平显著下降(P<0.05),血浆白蛋白水平显著升高(P<0.01),血脂水平显著下降(P<0.05)。治疗后组与正常组比较,除IL-2外,余各项指标均无显著性差异(P>0.05)。结论:在难治性肾病综合征患者体内存在IL-2、sIL-2R的异常,普乐可复对其有明确的抑制作用,从而调节T细胞活性,有效降低24小时尿蛋白,提高血浆白蛋白含量,降血脂,缓解难治性肾病综合征的病情。     

SLE患者T细胞和IL－2／IL－2R系统变化的临床意义

本文检测３７例（４１份）ＳＬＥ患者ＩＬ－２的产生、ｍＩＬ－２Ｒ的表达、ｓＩＬ－２Ｒ水平、淋巴细胞转化及Ｔ细胞亚群。结果表明：ＳＬＥ患者ｓＩＬ－２Ｒ水平升高，而ＩＬ－２的产生、ｍＩＬ－２Ｒ的表达、淋转率、ＣＤ４＋百分率和ＣＤ４＋／ＣＤ８＋比值均下降，由于其中仅有ｓＩＬ－２Ｒ水平与疾病活动性有关，因而ｓＩＬ－２Ｒ可作为疾病活动的一个指标。免疫指标的变化与激素治疗无关。本文认为Ｔ细胞功能及ＩＬ－２释放紊乱主要是由疾病本身的免疫调节紊乱引起。     

SLE患者T细胞和IL－2／IL－2R系统变化的临床意义

本文检测３７例（４１份）ＳＬＥ患者ＩＬ－２的产生、ｍＩＬ－２Ｒ的表达、ｓＩＬ－２Ｒ水平、淋巴细胞转化及Ｔ细胞亚群。结果表明：ＳＬＥ患者ｓＩＬ－２Ｒ水平升高，而ＩＬ－２的产生、ｍＩＬ－２Ｒ的表达、淋转率、ＣＤ４＋百分率和ＣＤ４＋／ＣＤ８＋比值均下降，由于其中仅有ｓＩＬ－２Ｒ水平与疾病活动性有关，因而ｓＩＬ－２Ｒ可作为疾病活动的一个指标。免疫指标的变化与激素治疗无关。本文认为Ｔ细胞功能及ＩＬ－２释放紊乱主要是由疾病本身的免疫调节紊乱引起。     

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.