氯氮平对不同病程女性精神分裂症患者血清白细胞介素 6及可溶性白细胞介素 6受体的影响

目的探讨女性精神分裂症患者血清白细胞介素 6(IL 6)、可溶性白细胞介素 6受体 (sIL 6R)治疗前后变化及其与抗精神病药物氯氮平血清水平的关系. 方法采用酶联免疫吸附法测定 40例女性精神分裂症患者 (病程≥ 5年组和病程 < 5年组,每组 20例 )治疗前及治疗后第 1、 2和 4周血清 IL 6和 sIL 6R水平,同时用高效液相色谱法测定氯氮平水平,以 20例女性健康者血清 IL 6、 sIL 6R水平作对照.治疗前与治疗后第 4周评定阴性和阳性症状量表 (PANSS)各一次. 结果①病程≤ 5年组患者治疗前血清 IL 6和 sIL 6R水平均显著高于正常对照组 (P< 0.01);治疗后第 1、 2和 4周血清 IL 6和 sIL 6R水平均显著低于对照组 (P< 0.01).②病程 >5年组患者治疗前及治疗后第 1,2和 4周血清 IL 6、 sIL 6R水平均显著低于正常对照组( P< 0.01).③除病程 >5年组患者第 1周血清 IL 6水平与氯氮平水平呈负相关( r=0.57,P< 0.01)外,余各时点血清 sIL 6R水平与氯氮平水平均无显著相关性( r=- 0.36～ 0.17,P >0.05).④氯氮治疗 4周后, PANSS减分率与 IL 6,sIL 6R减分率无显著相关( r=- 0.22～- 0.01,P >0.05). 结论女性精神分裂症患者血清 IL 6、 sIL 6R水平与健康女性差异显著 ,氯氮平对 IL 6和 SIL 6R有抑制作用,氯氮平的抗精神病作用可能与对 IL 6,sIL 6R的调节作用有关.     

脑出血后不同时间脑脊液中可溶性白细胞介素6受体的变化

背景在脑血管病脑损伤中有许多细胞因子的参与,而白细胞介素6(interleukin-6,IL-6)被认为在中枢神经系统中具有神经保护和神经营养作用,而脑出血急性期脑脊液可溶性IL-6受体(solubleinterleukin-6 receptor,sIL-6R)的研究国内外报道较少.目的研究脑出血急性期脑脊液中sIL-6R变化与继发性脑损伤的关系.设计病例对照研究.单位暨南大学医学院第五附属医院检验科、神经外科、神经内科联合进行课题研究.对象从1999-01/2003-12收治的脑出血患者627例中,选择经临床诊断和CT证实的自发性脑出血后48 h内入院的患者,并排除创伤性脑出血和其他脑血管疾病,符合以上标准的32例患者作为研究对象(脑出血组),其中脑实质出血破入脑室者23例,单纯脑实质出血者7例,单纯脑室出血2例.13例同期住院的非神经系统疾病就诊者为对照组.方法患者于入院后2 d内腰穿取脑脊液2 mL离心沉淀取上清液放-80℃超低温冰箱保存待测,12例患者出血后第1,2,3,5,10～13天进行动态观察.采用酶联免疫吸附试验(ELISA)测定对照组和脑出血患者脑脊液中sIL-6R含量.主要观察指标对照组和脑出血患者脑脊液中sIL-6R含量.结果13例对照组和32例脑出血急性期患者脑脊液中sIL-6R含量分别为(380.54±93.05)ng/L,(1 220.18±878.71)ng/L,两者之间差别有显著意义(t'=5.332 3,P＜0.05).脑实质出血破入脑室者sIL-6R水平[(1 350.79±762.63)ng/L]显著高于单纯脑实质出血者[(609.21±398.99)ng/L],差异有显著性意义(t=2.462 3,P＜0.05).脑出血第1天时sIL-6R水平已达最高(1 503.01±775.13)ng/L,此后仍维持在较高水平.结论脑出血急性期患者sIL-6R含量显著升高,与继发性脑损伤程度和炎症反应有关.     

细胞因子中白细胞介素1β、白细胞介素1Ra及γ-氨基丁酸B受体与癫痫的发病

目的:综述细胞因子中的白细胞介素1β、白细胞介素1Ra及γ-氨基丁酸B受体在癫痫发病中的作用及其与癫痫的关系。资料来源:应用计算机检索PubMed数据库1990-01/2006-10相关文章,检索词“epilepsy,IL-1β,IL-1Ra,GABABR”,并限定文章语言种类为English;同时计算机检索CNKI数据库1990-01/2006-10相关文章,检索词“癫痫,白细胞介素1β,白细胞介素1受体拮抗剂,γ-氨基丁酸B受体”,限定文章语言种类为中文。资料选择:对资料进行初审,纳入标准:①随机对照研究。②基础或临床研究。排除标准:重复研究、重复临床报道的文献、个案报告。资料提炼:共收集到51篇关于癫痫,白细胞介素1β,白细胞介素1受体拮抗剂,γ-氨基丁酸B受体的随机和未随机试验,30个试验符合纳入标准。资料综合:①癫痫的发病有免疫学机制参与。白细胞介素1作为一种重要的细胞因子,在中枢神经系统中的作用尤为突出,在一些神经系统疾病有不同程度的升高,内源性增高的白细胞介素1可明显促进这些疾病所导致的脑损伤。内源性细胞介素1β增多及外源性给予白细胞介素1β与癫痫的形成有密切关系。白细胞介素1受体拮抗剂是白细胞介素1受体的天然拮抗剂。白细胞介素1β与其受体结合后,通过细胞内信息传递途径,多环节调节中枢神经系统的兴奋性,最终影响癫痫的发病过程。②γ-氨基丁酸是中枢神经系统中最主要的抑制性神经递质,各类癫痫的发生几乎都与脑内γ-氨基丁酸的功能变化有关。结论:细胞因子中的白细胞介素1β、神经递质中的γ-氨基丁酸B受体在癫痫的发病过程中均起着重要的作用。但二者在癫痫发病机制中的关系有待于进一步研究。     

高位硬膜外阻滞对扩张型心肌病患者白细胞介素6及可溶性白细胞介素2受体的影响

背景扩张型心肌病患者血清中细胞因子明显升高,心肌组织中也有细胞因子mRNA的表达,通过高位硬膜外阻滞治疗可以阻断细胞因子参与的恶性循环,改善心功能. 目的观察扩张型心肌病患者经过高位硬膜外阻滞术治疗后白细胞介素6及可溶性白细胞介素2受体的变化. 设计病例-对照分析. 单位首都医科大学宣武医院的检验科,哈尔滨医科大学第一临床医院的检验科和心内科. 对象哈尔滨医科大学第一临床医学院心内科2001-10/2002-05的扩张型心肌病患者35例,随机分为高位硬膜外阻滞组和常规治疗组,高位硬膜外阻滞组22例,男15例,女7例;心功能Ⅱ级4例,Ⅲ级9例,Ⅳ级9例.常规治疗组13例,男11例,女2例;心功能Ⅱ级1例,Ⅲ级5例,Ⅳ级7例.同期选择本院的健康体检者21例,男13例,女8例. 干预扩张型心肌病患者分别采用高位硬膜外阻滞治疗及常规治疗,常规治疗组只采用常规治疗方法.所有患者于治疗前及治疗4周后清晨抽取空腹肘静脉血3 mL,酶联免疫吸附法测定血清中白细胞介素6和可溶性白细胞介素2受体水平. 主要观察指标各组患者血清中白细胞介素6和可溶性白细胞介素2受体水平. 结果56例观察对象的血样均合格,全部进入结果分析.①扩张型心肌病患者血清白细胞介素6水平(13.9 ng/L)明显高于健康对照组(11.22 ng/L),(z=-3.072,P＜0.05).②高位硬膜外阻滞治疗组治疗后白细胞介素6水平(11.42 ng/L)较治疗前(20.42 ng/L)明显下降(z=2.582 9,P＜0.05).常规治疗组治疗前后白细胞介素6水平相似(12.16 ng/L12.80 ng/L,z=-1.89,P＞0.05).高位硬膜外阻滞组治疗前后白细胞介素6水平差值(-2.04 ng/L)明显高于常规治疗组(0.28 ng/L),(z=3.182 9,P＜0.01).③扩张型心肌病组可溶性白细胞介素2受体水平[(1 306.17±1.46)ng/L]高于健康对照组[(1 078.95±1.23)ng/L],(t=2.51,P＜0.05).④高位硬膜外阻滞治疗组治疗后可溶性白细胞介素2受体水平[(1 086.68±1.34)ng/L]低于治疗前[(1 328.01±1.51)ng/L,(t=2.145,P＜0.05)].常规治疗组治疗前后可溶性白细胞介素2受体水平相似[(1473.33±1.66)ng/L(1 331.07±1.52)ng/L,t=-1.06,P＞0.05].结论高位硬膜外阻滞治疗后细胞因子白细胞介素6及可溶性白细胞介素2受体水平都明显下降,而常规治疗组未见此效果,表明高位硬膜外阻滞治疗对细胞因子有良好的调节作用,优于常规治疗.高位硬膜外阻滞对细胞因子的调节作用与其阻滞效应中的全面抑制心脏交感神经,抑制交感神经对体液免疫系统的激活及阻断其恶性循环有关.     

氯氮平对不同病程女性精神分裂症患者血清白细胞介素6及可溶性白细胞介素6受体的影响

目的：探讨女性精神分裂症患者血清白细胞介素6(IL-6)、可溶性白细胞介素6受体(sIL-6R)治疗前后变化及其与抗精神病药物氯氮平血清水平的关系。方法：采用酶联免疫吸附法测定40例女性精神分裂症患者(病程≥5年组和病程&;lt;5年组，每组20例)治疗前及治疗后第1、2和4周血清IL-6和sIL-6R水平，同时用高效液相色谱法测定氯氮平水平，以20例女性健康者血清IL-6、sIL-6R水平作对照。治疗前与治疗后第4周评定阴性和阳性症状量表(PANSS)各一次。结果：①病程≤5年组患者治疗前血清IL-6和sIL-6R水平均显著高于正常对照组(P&;lt;0．01)；治疗后第1、2和4周血清IL-6和sIL-6R水平均显著低于对照组(P&;lt;0．01)。②病程&;gt;5年组患者治疗前及治疗后第1，2和4周血清IL-6、sIL-6R水平均显著低于正常对照组(P&;lt;0．01)。③除病程&;gt;5年组患者第1周血清IL-6水平与氯氮平水平呈负相关(r=0．57，P&;lt;0．01)外，余各时点血清sIL-6R水平与氯氮平水平均无显著相关性(r=-0．36～0．17，P&;gt;0．05)。④氯氮治疗4周后，PANSS减分率与IL-6，sIL-6R减分率无显著相关(r=-0．22～-0．01．P&;gt;0．05)。结论：女性精神分裂症患者血清IL-6、sIL-6R水平与健康女性差异显著，氯氮平对IL-6和sIL-6R有抑制作用，氯氮平的抗精神病作用可能与对IL-6，sIL-6R的调节作用有关。     

外科感染患者白细胞介素－2的生成和白细胞介素－2受体的表达

观察了２２例外科感染患者的白细胞介素－２（ＩＬ－２）的生成和白细胞介素－２受体（ＩＬ－２Ｒ）表达的变化。结果：感染患者ＩＬ－２Ｒ表达明显降低，而手术和非手术治疗均能使ＩＬ－２Ｒ恢复正常；而感染患者淋巴细胞ＩＬ－２生成呈升高趋势，治疗后进一步升高。研究结果提示：淋巴细胞功能异常在外科感染的发生机制中起重要作用。     

白细胞介素—2及其受体与肺疾病

一、概述白细胞介素-2(Interleukin 2,IL-2)是活化的T淋巴细胞,主要为T辅助细胞所分泌的一种淋巴因子,含有133个氨基酸,分子量为15,420道尔顿的糖蛋白,由于它能维持T细胞在体外生长,故又名T细胞生长因子。此外,IL-2还能维持激活T细胞克隆和NK细胞克隆在体外继续繁殖及活化B细胞和巨噬细胞,使B细胞分泌抗体增加及增强巨噬细胞杀伤活性等,因而IL-2已成为机体免疫系统中极为重要的抗肿瘤、抗感染、抗衰老介质。目前用T淋巴细胞杂交瘤和基因工程技术可获得大量纯化的IL-2制品,称为重组IL-2(Recombinant IL-2 rIL-     

白细胞介素9

白细胞介素9(IL-9)是一种由激活的辅助性T细胞分泌的细胞因子。最早由Uytten-hove等从激活的小鼠Th细胞系TUC2.15培养上清中分离出来的。它能在无抗原及IL-2和IL-4情况下刺激TUC 2.15细胞增殖,根据其分于量初步命名为P40。1989年,Yang等表达了P40在人类中的同源因子,统一命名为白细胞介素9。现已发现其在造血调控,免疫应答和肿瘤发生等生理及病理生理过程中起的作用,引起人们的重视。     

大枣多糖对免疫抑制小鼠白细胞介素2及其受体水平的影响

目的：探讨大枣多糖对脾细胞产生和分泌白细胞介素2(interleukin-2,IL-2)和血清可溶性白细胞介素2受体(aoluble interleukin-2 receptor,SIL-2R)水平的影响，以及作用机制。方法：用放血与环磷酰胺并用致免疫低下小鼠为研究对象，分为大、中、小剂量(剂量分别为400，200，100mg／kg)的大枣多糖水溶液组，当归补血口服液组(6．6mL／kg，原药液稀释3倍)及同体积生理盐水组，另设完全空白对照组，每组6只。造模同时给药，连续7d，测定小鼠脾细胞IL-2的产生及活性和血清SIL-2R水平。结果：大、中、小剂量大枣多糖组和当归补血口服液组均可显著提高1：2和1：4稀释度免疫抑制小鼠脾细胞IL-2的产生和活性，与模型组比较，差异有显著性意义(t=5．2～8．4，P&;lt;0.01)，以中剂量大枣多糖组对免疫抑制小鼠脾细胞Ⅱ，2产生及活性影响作用为最强。大、中、小剂量大枣多糖组及当归补血口服液组均可显著降低血清SR-2R水平，与模型组比较，差异有显著性意义(t=14．1～16．3，P均&;lt;0．01)，以中剂量大枣多糖对血清SII，2R水平的影响为最显著。结论：大枣多糖可促进免疫抑制小鼠脾细胞产生和分泌IL-2，降低血清IL-2R水平。     

老年病人白细胞介素—2及其受体变化的初步研究

本文检测４０例健康献血员，２０例健康老人及８６例老年患者外周血白细胞介素２活性及血、尿中可溶性白细胞介素２受体的水平。结果显示老年人血白细胞介素２活性明显低于中青年人，可溶性白细胞介素２则明显高于青中年组，肿瘤及糖尿病患者尤为突出。尿可溶性白细胞介素２在老年患者亦升高但与白细胞介素２升高不呈比例。     

Balance of pro- and anti-inflammatory cytokines in liver surgery.

Inflammatory response in surgery is associated with the release of cytokines. Many cytokines are produced by macrophages; therefore surgical injuries to the liver may have great influence on the release of cytokines. Ischemia creates tissue injury and may contribute to the cytokine release. A balanced ratio of pro- and anti-inflammatory cytokines is important for appropriate immune response; excessive inflammation or hypo-responsiveness can lead to post-operative complications. To determine the magnitude of the cytokine response caused by liver surgery and to evaluate the balance of pro- and anti-inflammatory cytokines released during the operation, we measured levels of tumor necrosis factor-alpha (TNFalpha), interleukin (IL)-1beta, IL-6 and IL-10 in 19 patients undergoing liver resection. The results showed a continuous rise of IL-6 and a transient elevation of IL-10. Levels of TNFalpha remained low; IL-1beta was not detected at any sampling time. We conclude that liver surgery induces cytokine response characterized predominantly by an early appearance of IL-6 and IL-10, the elevation of IL-6 may be mainly caused by splanchnic ischemia. The IL-6/IL-10 ratio could possibly reflect the balance of pro- and anti-inflammatory cytokines in liver surgery better than the TNFalpha/IL-10 ratio, which can well represent inflammatory status in sepsis.     

Human eosinophils express functional interleukin 2 receptors.

Because T cell-derived cytokines may affect the functioning of eosinophils, we have investigated the capacity of human eosinophils to respond to IL-2. IL-2 was a potent chemoattractant with ED50 of 10(-12) M with eosinophils from all normal and eosinophilic donors tested. The monoclonal antibodies anti-Tac and TU27 against p55 (Tac/CD25) and p75 receptor subunits, respectively, each inhibited IL-2-dependent eosinophil migration. The molar potency of IL-2 and the inhibitory activity of each of the above antibodies suggest that high affinity heterodimeric IL-2 receptor complexes mediated the migration responses of eosinophils to IL-2. Binding of monoclonal antibody against p75 was not detectable by flow cytometry, and high affinity binding sites for 125I-IL-2 were below the limits of quantitation on eosinophils from individuals with eosinophilia. Expression of p55 (Tac/CD25) by eosinophils, without requirement for in vitro activation, was demonstrable by flow cytometry, radioimmunoprecipitation, and Northern blotting for mRNA. Surface expression of p55 on eosinophils from normal or eosinophilic individuals increased during culture for 24-48 h with a biologic activity purified from stimulated U937 cells and to a lesser extent with granulocyte-macrophage CSF or lymphocyte chemoattractant factor but not with nine other cytokines. These studies indicate that blood eosinophils respond to IL-2 and identify one mechanism whereby activation of T lymphocytes may influence the function of eosinophils.     

Expression of interleukin 2 receptors on activated human B cells

Using anti-Tac, a monoclonal anti-interleukin 2 (IL-2) receptor antibody, we have explored the possibility that certain activated B cells display receptors for IL-2. Resting normal B cells and unselected B cell lines established from normal individuals were Tac antigen negative. In contrast, the cell surface Tac antigen expression was demonstrable on 6 of 10 B cell lines from patients with Burkitt's lymphoma, 5 of 6 B cell lines derived from patients with HTLV-I- associated adult T cell leukemia (including all four that had integrated HTLV-I into their genome), and on certain normal B cells activated with pokeweed mitogen. Furthermore, cloned Epstein-Barr virus- transformed B cell lines derived from Tac-positive normal B cells continued to express the Tac antigen in long-term cultures and manifested high affinity IL-2 receptors identified in binding studies with purified radiolabeled IL-2. The line 5B4 developed in the present study could be induced with purified JURKAT-derived or recombinant IL-2 to express a larger number of IL-2 receptors. Furthermore, the addition of IL-2 to the 5B4 B cell line augmented IgM synthesis, which could be blocked by the addition of anti-Tac. The size of the IL-2 receptors expressed on the cloned normal B cell lines was similar (53,000-57,000 daltons) to that of receptors on phytohemagglutinin-stimulated T cell lymphoblasts. Thus, certain malignant and activated normal B cells display the Tac antigen and manifest high affinity receptors for IL-2. These data suggest that IL-2 may play a role in the differentiation of activated B cells into immunoglobulin-synthesizing and -secreting cells.     

Expression of interleukin 2 receptors by monocytes from patients with acquired immunodeficiency syndrome and induction of monocyte interleukin 2 receptors by human immunodeficiency virus in vitro.

A population of circulating mononuclear cells from patients with AIDS was identified which expressed interleukin 2 receptors (IL-2R). By dual-fluorescence flow microfluorometry, the patients' IL-2R+ cells were further identified as Leu M3+ monocytes (29.4 +/- 5.2% of the Leu M3+ cells were IL-2R+, n = 15), whereas Leu M3+ monocytes from normal subjects were IL-2R negative (2.0 +/- 0.42%; P less than 0.001). By Northern analysis, monocytes from AIDS patients, but not control subjects, constitutively expressed steady-state levels of IL-2R mRNA. Functionally, the IL-2R+ monocytes were capable of depleting IL-2 from culture supernatants, suggesting a mechanism for the reduced IL-2 levels commonly seen in AIDS patients. IL-2R+ monocytes also expressed increased levels of surface HLA-DR which may favor monocyte T-cell interactions and the transmission of human immunodeficiency virus (HIV). In additional studies, normal monocytes were infected with a macrophage-tropic HIV isolate in vitro and monitored for IL-2R and HLA-DR expression. Within 24-48 h after exposure to HIV in vitro, but before evidence of productive infection, greater than 25% of the monocytes became IL-2R+ with increasing numbers of IL-2R+ cells and HLA-DR levels through day 6. These early signaling effects of HIV could be mimicked by adding purified HIV envelope glycoprotein gp120 to the monocytes. This stimulation of monocytes before or independent of productive infection of the cells by HIV is consistent with in vivo observations of activated and/or abnormal functions by monocytes that do not appear to be infected with HIV in AIDS patients.     

Reconstitution of the functional receptors for murine and human interleukin 5

The murine interleukin 5 receptor (mIL-5R) is composed of two distinct subunits, alpha and beta. The alpha subunit (mIL-5R alpha) specifically binds IL-5 with low affinity. The beta subunit (mIL-5R beta) does not bind IL-5 by itself, but forms the high-affinity receptor with mIL-5R alpha. mIL-5R beta has been revealed to be the mIL-3R-like protein, AIC2B which is shared with receptors for IL-3 and granulocyte/macrophage colony-stimulating factor. We demonstrated here the reconstitution of the functional receptors for murine and human IL- 5 on the mouse IL-2-dependent cell line, CTLL-2. CTLL-2 was transfected with the cDNAs for mIL-5R alpha and/or AIC2B. Only CTLL-2 transfectant expressing both mIL-5R alpha and AIC2B expressed the high-affinity receptor and proliferated in response to murine IL-5. Then CTLL-2 was transfected with the cDNAs for hIL-5R alpha and/or KH97 (beta c), the human homologue of AIC2B. Though beta c did not contribute much to binding affinity of hIL-5R, only CTLL-2 transfectant expressing both hIL-5R alpha and beta c proliferated in response to human IL-5. These results showed that the beta subunit is indispensable in IL-5 signal transduction. We further investigated the function of IL-5-specific alpha subunit in transmitting IL-5 signals. Mutant mIL-5R alpha, which lacks its whole cytoplasmic domain, was transfected into mouse IL-3- dependent cell line, FDC-P1 expressing AIC2B intrinsically. The resulting transfectant did not respond to IL-5, though the transfectant expressed the high-affinity IL-5R, indicating that the cytoplasmic portion of the alpha subunit also has some important role in IL-5- mediated signal transduction.     

白细胞介素8及其受体在急性白血病的表达及其意义

目的探讨白细胞介素８（ＩＬ８）及其Ａ、Ｂ受体（ＩＬ８ＲＡ、ＩＬ８ＲＢ）的表达与急性白血病（ＡＬ）的分型、疗效及并发症的关系。方法用酶联免疫夹心法检测７７例初诊ＡＬ患者外周血ＩＬ８含量,用间接免疫荧光及流式细胞术检测骨髓单个核细胞（ＭＮＣｓ）表达ＩＬ８Ｒ,并检测了１５例ＡＬ完全缓解（ＣＲ）期脑脊液（ＣＳＦ）中ＩＬ８水平。结果ＡＬ患者外周血ＩＬ８水平高于正常人,其中急性髓系白血病（ＡＭＬ）高于急性淋巴细胞白血病（ＡＬＬ）,Ｍ４、Ｍ５高于Ｍ１～Ｍ３,ＢＡＬＬ高于ＴＡＬＬ（Ｐ＜０．０５）。ＡＬＬ中ＩＬ８＞１００ｎｇ／Ｌ组比≤１００ｎｇ／Ｌ组疗效差（Ｐ＜０．０５）;约３６．３６％的ＡＬ患者ＩＬ８Ｒ（＋）,ＩＬ８Ｒ（＋）者的外周血白细胞计数及幼稚细胞比例显著高于ＩＬ８Ｒ（－）者（Ｐ＜０．０５）;ＣＲ期患者ＣＳＦ中ＩＬ８水平与治疗前比较,差异无显著性（Ｐ＞０．０５）,合并中枢神经系统白血病（ＣＮＳＬ）时明显升高。结论外周血和ＣＳＦ中ＩＬ８水平的检测及检测骨髓ＭＮＣｓ膜ＩＬ８Ｒ的表达有助于ＡＬ各亚型的鉴别及预后判断;ＣＮＳＬ发生时ＣＳＦ中ＩＬ８增高。     

Expression of interleukin 2 receptors and binding of interleukin 2 by gamma interferon-induced human leukemic and normal monocytic cells

Gamma interferon induced surface expression of interleukin 2 (IL-2) receptors on normal human monocytes and the monocytoid cell lines U937 and HL60. These receptors were detected by anti-IL-2 receptor monoclonal antibodies, and U937 IL-2 receptors were indistinguishable from T lymphocyte IL-2 receptors by immunoprecipitation. Also, U937 IL- 2 receptors bound biologically active IL-2. These results suggest a role for monocyte IL-2 receptors in T cell/monocyte interaction during an immune response.     

Transient expression of interleukin 2 receptors. Consequences for T cell growth

T lymphocyte mitosis results from the interaction of interleukin 2 (IL- 2) with specific receptors that appear only after appropriate immune stimulation. To assess the potential role of IL-2 receptor levels in determining the rate and magnitude of T cell proliferation, the expression of IL-2 receptors by lectin-stimulated human peripheral blood T cells was examined and correlated with T cell growth. Using biosynthetically radiolabeled IL-2 and anti-Tac, a monoclonal antibody that blocks IL-2 receptor binding, IL-2 receptors were found to accumulate slowly and asynchronously among lectin-stimulated T cells and to precede the onset of DNA synthesis. Moreover, a critical threshold of IL-2 receptor density appeared to be required before the commitment to cell cycle progression, as analyzed quantitatively by tritiated thymidine incorporation and flow cytometric analysis of cellular DNA content. Once maximal IL-2 receptor expression occurred, continued proliferation was IL-2 concentration dependent as assessed using homogenous immunoaffinity-purified IL-2. Upon removal of the activating lectin, IL-2 receptor levels progressively declined, and, in parallel, the rate of proliferation diminished. The decay of IL-2 receptors could not be attributed to IL-2-mediated down-regulation. Instead, renewed IL-2 receptor expression was dependent upon the reintroduction of the initial activating signal. Repetitive exposure to lectin resulted in a more rapid reexpression of maximal IL-2 receptor levels, which was then followed by an accelerated resumption of proliferation. Thus, the extent of T cell proliferation after immune stimulation depends upon the interplay of the IL-2 concentration available and the density of IL-2 receptors expressed, both of which are ultimately determined by antigen/lectin stimulation. The awareness of the transience and the antigen/lectin dependence of IL-2 receptor expression, together with the capacity to monitor T cell cultures for IL-2 receptor levels, should facilitate the initiation and maintenance of cloned, antigen-specific T cells in long-term culture. In addition, these findings suggest that, in vivo, the rapidity of acquisition of maximum IL-2 receptor levels by activated T cells and the duration of IL-2 receptor expression may well direct the magnitude of T cell clonal expansion and resultant immune responses.     

Changes in plasma cytokines and their soluble receptors in complex regional pain syndrome

Complex Regional Pain Syndrome (CRPS) is a chronic and often disabling pain disorder. There is evidence demonstrating that neurogenic inflammation and activation of the immune system play a significant role in the pathophysiology of CRPS. This study evaluated the plasma levels of cytokines, chemokines, and their soluble receptors in 148 subjects afflicted with CRPS and in 60 gender- and age-matched healthy controls. Significant changes in plasma cytokines, chemokines, and their soluble receptors were found in subjects with CRPS as compared with healthy controls. For most analytes, these changes resulted from a distinct subset of the CRPS subjects. When the plasma data from the CRPS subjects was subjected to cluster analysis, it revealed 2 clusters within the CRPS population. The category identified as most important for cluster separation by the clustering algorithm was TNFα. Cluster 1 consisted of 64% of CRPS subjects and demonstrated analyte values similar to the healthy control individuals. Cluster 2 consisted of 36% of the CRPS subjects and demonstrated significantly elevated levels of most analytes and in addition, it showed that the increased plasma analyte levels in this cluster were correlated with disease duration and severity. PERSPECTIVE: The identification of biomarkers that define disease subgroups can be of great value in the design of specific therapies and of great benefit to the design of clinical trials. It may also aid in advancing our understanding of the mechanisms involved in the pathophysiology of CRPS, which may lead to novel treatments for this very severe condition.