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1.
Immune activation is central to many immune disorders. Clinical investigations have shown that immune activation can be quantified by measurements of soluble immune activation products in serum. Most in vitro studies of these immune activation products have focused on single products. In this study the specific cell sources and the major lymphokines inducing multiple activation products were investigated. In vitro addition of interferon-gamma (IFN-gamma) or IL-2 stimulated peripheral blood mononuclear cells to produce neopterin, beta 2-microglobulin (beta 2-M) and soluble IL-2 receptor (sIL-2R). These two lymphokines can act independently, because neutralizing antibodies to one of the lymphokines did not block the inducing activity of the other. Tumour necrosis factor-alpha (TNF-alpha) was also investigated and shown to be a less powerful inducer than IL-2 or INF-gamma. Separated lymphoid subpopulations responded differently to specific lymphokines. Monocytes produced only neopterin and only in response to INF-gamma. T cells released beta 2-M and sIL-2R in response to IL-2. B cells, however, were capable of producing all three immune activation products. Neopterin production in B cells was induced by either INF-gamma of IL-2, indicating that B cells have additional mechanisms for responding to lymphokines. To investigate whether these in vitro findings also occur in vivo, sera from patients who had received either rIL-2 or INF-gamma treatment were tested. INF-gamma administration led to substantial increases in serum neopterin but only a moderate beta 2-M increase and no increase in the serum sIL-2R levels. rIL-2 administration caused a substantial increase of all three serum immune activation products, consistent with our in vitro findings. The results confirm that increased serum levels of soluble immune activation products are indicators of increased cytokine production by lymphocytes and monocytes and also that B cells can be a prominent source of immune activation products.  相似文献   

2.
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。  相似文献   

3.
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.  相似文献   

4.
A general consensus that thermal injury affects T lymphocyte function adversely is supported particularly by the observation that burned patients' lymphocytes secrete reduced levels of biologically active IL-2 in vitro. In the same patients, however, high serum concentrations of the low-affinity IL-2 receptor (IL2R alpha), a product of an IL-2-activated gene, have been observed. In this study a significant proportion of patients also demonstrated over-physiological levels (from 2 to 500 U/ml) of serum IL-2 ascertained by immunoassay. Increases in serum IL-2 content correlated significantly (P less than 0.02) with those of serum IL-2R alpha during the first week post-burn. Later, serum IL-2R alpha levels continued to increase up to 30 days while IL-2 eventually declined. Thus, augmented secretion of IL-2R alpha appears related to the high serum IL-2 content. Therefore refractoriness to further immune stimulation may be due to early activation of the lymphoid system, rather than to an intrinsic incapacity of T lymphocytes for generating sequential responses.  相似文献   

5.
Soluble plasma IL-2 receptors and malaria.   总被引:2,自引:2,他引:2       下载免费PDF全文
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.  相似文献   

6.
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。  相似文献   

7.
SLE患者T细胞和IL-2/IL-2R系统变化的临床意义   总被引:1,自引:0,他引:1  
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。  相似文献   

8.
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.  相似文献   

9.
为了研究抗卵巢抗体(AOAb)对卵巢组织内细胞分泌功能的影响,分别将AOAb阳性、阴性血清γ球蛋白与卵巢组织细胞共培养,收集培养液,测定IL-1β、TNF-α、sIL-2R、E_2和P水平。结果表明,与对照组比较,经AOAb阳性血清γ球蛋白作用后卵巢组织细胞培养液中,IL-1β、TNF-α和sIL-2R水平显著增加(P<0.01),E_2和P含量明显降低(P<0.01)。  相似文献   

10.
These studies were undertaken with the purpose of elucidating the key signals involved in the regulation of the production of soluble interleukin-4 receptors (sIL-4R) in mice during Th1 and Th2 responses to infection with the parasite Leishmania major. Our results showed that the production of sIL-4R was consistently higher in lymph node cell cultures from animals mounting a predominant Th2 response (BALB/c mice), and that sIL-4R production paralleled that of IL-4 in both mouse strains, even in the presence of a dominant Th1 response (C3H/FeJ mice). Consistently, administration of anti-IL-12 antibodies to infected C3H/ FeJ mice induced a switch from a Th1- to a Th2-type response and resulted in enhanced production of sIL-4R. Addition of rIL-12 to splenic cell cultures, however, was found not to have a direct effect on sIL-4R production induced by IL-4 or T cell mitogens. Moreover, the production of sIL-4R appears to be little influenced by Th1-produced cytokines, inasmuch as recombinant interferon-gamma or supernatants derived from antigen-stimulated Th1 clones did not affect the production of sIL-4R by activated splenic cultures. Despite its correlation with Th2 responses, the presence of IL-4 was not an absolute requirement for the up-regulation of the expression of sIL-4R because increased levels could be induced on cells obtained from IL-4-/- mice. These results indicate that, although enhanced sIL-4R production is a feature related to the activation and/or generation of Th2 responses, it is not absolutely dependent on IL-4 or directly inhibited by IL-12 or Th1 cytokines.  相似文献   

11.
Previous studies have shown that exogenous IL-2 does not correct the reduction in phytohaemagglutinin (PHA)-induced proliferation of lymphocytes from HIV-1 infected (HIV+) individuals. We investigated the mechanism of this reduction to determine if reduced expression of the complete IL-2 receptor (IL-2R) was responsible. In a series of experiments, PHA-stimulated lymphocytes from a total of 89 HIV- and 93 HIV+ homosexual men from the Baltimore Multicentre AIDS Cohort Study (MACS) were studied to determine the expression of messages for the alpha and beta subunits of the IL-2R, the binding of 125I-IL-2 to high affinity IL-2R, and the effect of IL-2 on cell proliferation. Compared to HIV- donors, PHA-stimulated lymphocytes from most HIV+ donors demonstrated (i) a reduction in high affinity IL-2R expression that correlated with the reduction in the IL-2-induced proliferative response; and (ii) a reduction in expression of both IL-2R alpha- and beta-chain mRNA which may be responsible for decreased high affinity IL-2R expression. However, lymphocytes from some HIV+ individuals had borderline low IL-2-induced proliferation despite normal or elevated expression of high affinity IL-2R. These results suggest that decreased expression of IL-2R may account, at least in part, for the lower proliferative response of cells from HIV+ donors.  相似文献   

12.
The effect of dose and schedule of continuous i.v. rIL-2 infusions on leucocyte subset counts, activation status of CD56+CD3- natural killer (NK) and CD3+ T lymphocytes, and cytolytic activities of peripheral blood mononuclear cells (PBMC) was studied. A single 4-day course of rIL-2 in escalating doses (0.9-11.5 x 10(6) U/m2 per day) was given to 18 patients with various types of metastatic cancer. The serum IL-2 concentration during rIL-2 therapy ranged between 23 and 64 U/ml and was proportional to the administered rIL-2 dose, as was the rebound lymphocytosis following therapy. Before therapy, the CD56+CD3- NK cells expressed low levels of the p75 chain of the IL-2 receptor (IL-2R) and virtually no IL-2R(p55). Most CD3+ T cells were IL-2R(p55-,p75-). Between 2 and 4 days following therapy, i.e. at the time of lymphocytosis, the percentage of CD56+,CD3- NK cells among the lymphocytes had increased proportional to the administered rIL-2 dose. The levels of IL-2R(p75) expression by the CD56+,CD3- NK cells had increased. The percentages of CD3+ T cells expressing IL-2R(p55), HLA-DR and CD45RO had increased proportional to the administered rIL-2 dose. The level of lymphokine- activated killer (LAK) activity against Daudi cells was also positively correlated with rIL-2 dose. Subsequently, seven patients received 4-weekly cycles of rIL-2 (2.9-4.4 x 10(6) U/m2 per day) during 4 consecutive weeks. This schedule led to marked increments in lymphocyte and eosinophil counts, and to increased cytolytic activities compared with pretreatment. We conclude that CD56+,CD3- NK and CD3+ T cells are activated differentially by continuous i.v. rIL-2 proportional to dose and duration of treatment.  相似文献   

13.
We examined the mode of action of different immunosuppressants on the responsiveness of phytohemagglutinin (PHA)-induced lymphoblasts further stimulated by recombinant interleukin-2 (rIL-2). The stimulation of PHA blasts with rIL-2 resulted in an enhancement of tritiated thymidine ([3H]TdR) incorporation and of soluble interleukin-2 receptor (sIL-2R) release. Cyclosporin A (CsA) and prednisolone inhibited in different ways the responsiveness of PHA pre-stimulated blood mononuclear cells (PBMC) to rIL-2, as measured by [3H]TdR incorporation. The addition of CsA resulted in considerable enhancement of the release of sIL-2R, whereas the addition of prednisolone was associated with a similar enhancement only when the higher concentrations of rIL-2 were employed. EGTA, a calcium (Ca2+) chelator, and verapamil, a Ca2+ channel blocker, inhibited [3H]TdR incorporation in a concentration-dependent manner. EGTA inhibited sIL-2R release in the same manner when used alone, and reversed the CsA- and prednisolone-induced enhancement of sIL-2R release by rIL-2 induced lymphoblasts, when used in combination with CsA or prednisolone. Verapamil had a similar but less striking effect. The effects of CsA and prednisolone were also studied in PHA-induced blasts originating from purified CD4+ or CD8+ lymphocytes. Stimulation of these blasts with rIL-2 resulted in higher [3H]TdR incorporation by CD8+ blasts than by CD4+ blasts: however, no sIL-2R release was detected in supernatants of either CD4+ or of CD8+ blasts. Both CsA and prednisolone inhibited the rIL-2-induced enhancement of [3H]TdR incorporation by both T-cell subsets.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

14.
PHA-LAK细胞激活培养过程中多项免疫学指标的动态分析   总被引:5,自引:1,他引:5  
本文用APAAP、ELISA、MTT等方法检测了PHA—LAK细胞激活培养过程中某些免疫学指标的动态变化,结果表明:(1)在PHA-LAK细胞预刺激阶段,CD3~+、CD4~+、CD8~+及mIL-2Ra~+细胞百分率均持续升高(P均<0.01);上清液中sIL-2R水平和IL-2活性也升高,且前者与MIL-2Ra~+细胞百分率呈正相关(r=0.84,P<0.05);(2)在rIL2激活培养阶段,CD3~+、mIL-2Ra~+细胞百分率居高不下,CD4~+细胞百分率逐渐降低,而CD8~+细胞百分率则逐渐升高,培养上清液中sIL-2R水平增加和IL-2活性降低的幅度以激活培养的初期(0~3d)为最大.从而提示PBMC经预刺激后可迅速被外源性的rIL-2激活,这不仅可以提高rIL-2的利用率,也可能是PHA-LAK细胞具有较高增殖能力和细胞毒活性的原因.  相似文献   

15.
Sera from nine Sicilian patients with confirmed visceral leishmaniasis (Leishmania donovani infantum; VL), at the moment of the diagnosis, during the course of the disease and after clinical recovery, were analysed for the concentration of soluble IL-2 receptor (sIL-2R). The results show that sIL-2R is a marker of disease activity, since it is in high concentration at the beginning of infection and returns to the normal range following successful chemotherapy. At the same time of serum analysis for sIL-2R, peripheral blood mononuclear cells (PBMC) of VL patients were stimulated with phytohaemagglutinin (PHA) or antigen and supernatant tested for IL-2 and interferon-gamma (IFN-gamma) production. Data demonstrate that there is an inverse relation between concentration of IL-2 and IFN-gamma in the supernatants and sIL-2R secretion in the sera.  相似文献   

16.
本文报道20例作维持性血液透析的慢性肾功能衰竭患者,其血清sIL-2R水平以及静息期和诱导后表达mIL-2R的活化T淋巴细胞百分率,均明显高于正常人对照组,患者经一次血透后即时检测,sIL-2R和静息期mIL-2R两种指标的水平均呈显著降低。此外,血透后血中IL-2水平较血透前增高。结果提示,慢性肾功能衰竭患者存在IL-2及其相应受体水平的异常,而充分透析能予以部分纠正。  相似文献   

17.
Cardiac surgery with cardiopulmonary bypass (CPB) leads to a systemic inflammatory response with secretion of cytokines. Alterations in the serum concentrations of cytokines have important prognostic significance. Reports on cytokine release during cardiac surgery with CPB have yielded conflicting results. Haemodilution occurs with the onset of CPB resulting in large fluid shifts during the perioperative course of cardiac procedures. In the present study we compare the perioperative course of serum concentrations of TNF-alpha, IL-1beta, IL-6, IL-10 and sIL-2R with and without correction for haemodilution in patients undergoing coronary artery bypass grafting (CABG) surgery. Twenty male patients undergoing elective CABG surgery with CPB and general anaesthesia using a balanced technique with sufentanil, isoflurane and midazolam were enrolled into the study. Serum levels of TNF-alpha, IL-1beta, IL-6, IL-10 and sIL-2R were measured using commercially available ELISA kits. Simultaneous haematocrit values were obtained at all sample times. Statistical analysis was performed by non-parametric analysis of variance and t-tests for data corrected for haemodilution and data that were not corrected for haemodilution. Adjusted significance level was P < 0.01. Intra-operatively, up to the second post-operative day PCV values were significantly decreased compared with preoperative values. Cytokine measurements not corrected for haemodilution were significantly lower than the corrected values. The perioperative haemodilution and decrease in PCV may lead to an underestimation of the cytokine secretion in post-operative patients. We conclude that cytokine measurements were significantly influenced by the perioperative haemodilution and the subsequent decrease in PCV and may in part account for the varying results reported in the literature regarding cytokine release in patients undergoing CABG surgery.  相似文献   

18.
Interleukin 2 (IL-2) plays a central role in the immune response and may be involved in the derangement of cellular immunoregulation of idiopathic IgA nephropathy (IgAN). The aim of this study was to investigate the serum levels and production of IL-2 from peripheral blood mononuclear cells (PBMC) and the distribution of IL-2 receptor cells and serum-soluble IL-2 receptor cells (sIL-2R) in patients with IgAN. Twenty-four patients with IgA nephropathy and 11 healthy controls (age and sex matched) were studied during an infection-free period without signs of clinical activity at the moment of the study. Serum IL-2 concentrations did not differ between patients and controls. The supernatant levels of IL-2 taken from 24-hr cultures of PBMC stimulated with phytohemagglutinin or tumor necrosis factor increased significantly in the patients but not in the controls. The percentage of IL-2R positive cells (CD25+) was increased in patients compared with controls. Moreover, IgAN patients had increased activated CD4+ lymphocytes when compared with the controls. Serum levels of sIL-2R were significantly higher in patients than in controls. There were no correlations among renal function, serum IgA levels, and urinary findings with cellular subsets or with IL-2 levels. However, sIL-2R was higher in the subgroup of patients with episodic macrohematuria and was closely related with the presence of red blood cells in the urinary sediment. We conclude that PBMC of IgA nephropathy patients have an overproduction of IL-2 after mitogenic stimulation, an increased helper T cell activity, increased IL-2R+ cells, and elevated serum levels of sIL-2R. These alterations are present in periods of apparent clinical inactivity. Finally, sIL-2R is closely related with hematuria, providing a good marker for disease activity. Our results suggest a pivotal role of IL-2 in cellular immune responses with regard to T cell activation in patients with IgAN.  相似文献   

19.
The soluble IL-6 receptor (sIL-6R) is generated through either proteolytic shedding of the cognate receptor (PC-sIL-6R), or released as the product of differential mRNA splicing (DS-sIL-6R). Using monocytic THP-1 cells, we demonstrate that both mechanisms are independently regulated, and that each process contributes to sIL-6R production. Shedding of the IL-6R was activated by the Ca2+ ionophore, ionomycin, and inhibited by the TNF-α protease inhibitor (TAPI). In contrast, basal sIL-6R release was unaffected by Ca2+ depletion and largely insensitive to TAPI. Moreover, although IL-6R shedding was inactivated by serum starvation, non-stimulated production remained intact. Basal sIL-6R production via differential mRNA splicing was shown through the inhibitory action of brefeldin A and an enzyme-linked immunosorbent assay specific for DS-sIL-6R. Release of this isoform was unaffected by ionomycin or TAPI, indicating that Ca2+ mobilization activates PC-sIL-6R generation, but not DS-sIL-6R. The divergent control of these sIL-6R isoforms indicates that they may independently influence the inflammatory response.  相似文献   

20.
大隐静脉曲张光凝治疗后血清IL-2和sIL-2R的测定   总被引:1,自引:0,他引:1  
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。  相似文献   

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