用干扰素－α治疗慢性丁型肝炎使HBsAg消失

用干扰素－α治疗慢性丁型肝炎使ＨＢｓＡｇ消失［英］／［ＬａｕＪＹＮ．．．ＭｅｄＶｉｒｏｌ．－１９９３，２９２．－３９］１１例丁型肝炎病毒（ＨＤＶ）引起的慢性活动性肝炎患者，经肝活检有ＨＤＶ抗原。这些患者随机使用干扰素α２ｂ治疗和对照试验。９例有静脉注...     

人巨细胞病毒感染对肾移植受者血清sIL－2R水平的影响

用ＰＣＲ检测ＨＣＭＶ－ＤＮＡ，ＥＬＩＳＡ法检测ＨＣＭＶ－ＩｇＭ及ＩｇＧ，以诊断肾移植受者ＨＣＭＶ感染。用双抗体夹心法ＥＬＩＳＡ检测６５例肾移植受者血清ｓＩＬ－２Ｒ水平，结果表明：ＨＣＭＶ感染后宿主血清ｓＩＬ－２Ｒ水平明显增高（Ｐ＜０．０１），且ＨＣＭＶ疾病组ｓＩＬ－２Ｒ增高程度大于无症状感染组（Ｐ＜０．０１）；６例原发性ＨＣＭＶ感染者ｓＩＬ－２Ｒ水平与ＩｇＭ水平呈正相关（ｒ＝０．９９０８），提示随感染程度增加，血清ｓＩＬ－２Ｒ水平随之增高，还发现血清ｓＩＬ－２Ｒ水平与Ｃ９４／ＣＤ８比值是负相关（ｒ＝－０．９７８９），说明ＨＣＭｖ感染后ｓＩＬ－２Ｒ水平增高与Ｔ细胞亚群改变有关，反之也说明ｓＩＬ－２Ｒ增高程度可表明体内免疫抑制状态。对于ＨＣＭＶ感染后血清ｓＩＬ－２Ｒ水平增高的机理有待进一步探讨。     

肝硬化患者血清透明质酸含量与sIL－2R水平的观察

本文用放射免疫测定法及双抗体夹心法测定了２５例健康人，３０例肝硬化患者血清透明质酸（ＨＡ）的含量及可溶性白细胞介素２受体（ｓＩＬ－２Ｒ）水平。结果表明：（１）肝硬化组血清ＨＡ含量及ｓＩＬ－２Ｒ水平均高于对照组（Ｐ值均＜０．０１）；（２）肝硬化组血清ＨＡ与ｓＩＬ－２Ｒ水平间呈正相关关系（ｒ＝０．５１９２，Ｐ＜０．０１）。提示：肝硬化组患者血清ｓＩＬ－２Ｒ水平增高与肝损害程度有关，可能是由于肝细胞受损而对ＳＩＬ－２Ｒ清除能力降低所致。     

呼吸道合胞病毒下呼吸道感染对机体细胞免疫的影响

为研究呼吸道合胞病毒（ＲＳＶ）急性下呼吸道感染（ＡＬＲＩ）的细胞免疫变化，对２５例病儿外周血白细胞介素２（ＩＬ－２）和可溶性白细胞介素２受体（ｓＩＬ－２Ｒ）水平、Ｔ细胞白细胞介素２受体（ＩＬ－２Ｒ）表达率和Ｔ细胞亚群百分率进行检测。结果显示，急性期病儿外周血ＩＬ－２水平明显低于恢复期和正常对照组，Ｔ细胞ＩＬ－２Ｒ表达率亦明显降低，而ｓＩＬ－２Ｒ水平却显著增高。急性期病儿ＩＬ－２水平与Ｔ细胞ＩＬ－２Ｒ表达率和ＣＤ＋４细胞百分率呈正相关，与ｓＩＬ－２Ｒ水平和ＣＤ＋８细胞百分率呈负相关；ｓＩＬ－２Ｒ水平与Ｔ细胞ＩＬ－２Ｒ表达率呈负相关，与临床严重程度呈正相关。上述各项免疫指标异常均提示ＲＳＶ感染时机体存在细胞免疫功能紊乱。     

慢性乙型肝炎,肝硬化患者外周血LAK细胞活性和sIL—2R测定的意义

采用＾３Ｈ－ＴｄＲ释放法测定５１例慢性肝病患者（ＣＰＨ１０例、ＣＡＨ２３例、ＬＣ１８例）外周血ＬＡＫ细胞活性，并用酶联法测定患者血清中ｓＩＬ－２Ｒ含量；与２９例正常对照组比较，发现肝病患者ＬＡＫ活性降低，ＨＢＶＤＮＡ阳性组ＬＡＫ活性较阴性组低（Ｐ〈０．０５），ｓＩＬ－２Ｒ增高，且慢性肝病组ＬＡＫ活性与ｓＩＬ－２Ｒ水平呈负相关，说明ＬＡＫ活性与机体免疫功能状态有关，ＨＢＶ的复制和高浓度的ｓＩＬ－２Ｒ     

丁型肝炎病人肝组织HDVRNA与 HBVDNA的表达及关系

目的 探讨丁型肝炎病人肝组织中ＨＤＡｇ、ＨＤＶＲＮＡ与ＨＢＶＤＮＡＧ表达及关系。方法 应用免疫组化和原位杂交技术检测了７９全丁型肝炎病人肝组织ＨＤＡｇ、ＨＤＶＲＡＮ～ＨＢＶＤＮＡ表达,以５２例型肝炎病人肝组织作对照。结果 丁型肝炎ＨＢＶＤＮＡ检出率（２７％）低于乙型肝炎（４４％）（Ｐ〈０．０５）。在坏死灶边缘肝细胞和气球样变肝细胞浆内有大量的ＨＤＶＲＮＡ蓄积或ＨＤＡｇ呈强型强表达,ＨＤＶＲＮＡ表达     

乙型和丙型肝炎病毒重叠感染者外周血可溶性白细胞介素2受体的检测与分析

应用单克隆抗体夹心酶联免疫吸附试验（ＥＬＩＳＡ）对７５例乙型肝炎病毒（ＨＢＶ）和丙型肝炎病毒（ＨＣＶ）重叠感染者血清的白细胞介素２受体（ｓＩＬ－２Ｒ）进行检测，并与单纯乙型肝炎病毒感染者和健康人做对照进行比较。结果显示，重叠感染者：ＩＬ·２Ｒ含量（７６３：：１１７．３Ｕ／ｍｌ）明显高于正常对照（Ｐ＜０，０ａ），但与乙型肝炎组比较无显著性差异，Ｐ＞０，０５。证实ＨＢＶ、ＨＣＶ重叠感染时机体免疫功能处于紊乱状态。ｓＩＬｌ２Ｒ升高的重要原因可能是与之结合的白细胞介素２（ｔＬ。２）产生受抑制或ｓＩＬ。２Ｒ产生过量所致，本研究还发现重叠感染的各；陆床型肝病【ＨＣＣ、ＬＣ、Ｃ５Ｈ、ＡＨ、ＣＰＨ）ｓｌＬ－２Ｒ含量以ＨＣＣ、ＬＣ、ＣＳＨ含量最高，ＡＨ最低。显示ｓＩＬ．２Ｒ含量消长与疾病严重程度呈正相关（Ｐ＜０．０１），证实临床检测ｓＩＬ．２Ｒ水平对判定病情变化和愈后有显著名义，亦可评估机体免疫状态。     

肝硬化患者清透明质酸含量与sIL—2R水平的观察

本文用放射免疫测定法及双抗体夹心法测定了２５例健康人，３０例肝硬化患者血清透明质酸（ＨＡ）的含量及可溶性白细胞介素２受体（ｓＩＬ－２Ｒ）水平。结果表明：（１）肝硬化组血清ＨＡ含量及ｓＩＬ－２Ｒ水平间呈正相关关系（ｒ＝０．５１９２，Ｐ〈０．０１）。提示：肝硬化组患者血清ｓＩＬ－２Ｒ水平增高与肝损害程度有关，可能是由于肝细胞受损而对ｓＩＬ－２Ｒ清除能力降低所致。     

慢性HCV感染病人血清sIL－2R水平及干扰素γ的作用

慢性ＨＣＶ感染病人血清ｓＩＬ－２Ｒ水平及干扰素γ的作用［英］／ＪｕｎＨ…／／ＤｉｇＤｉｓＳｃｉ．一１９９５．４０（８）．一１８３７～１８４１为了探讨慢性ＨＣＶ感染病人血清中可溶性ＩＬ－２受体（ｓＩＬ－２Ｒ）的作用特点，文章检测了慢性ＨＣＶ感染病人血清...     

重型乙型肝炎血清可溶性白细胞介素2受体及外周血T淋巴细胞亚群的相关性

对２１例重型乙型肝炎患者白细胞介素２受体（ｓＩＬ－２Ｒ）及Ｔ淋巴细胞亚群检测发现，急性及亚急性重型、慢性重型肝炎患者的ｓＩＬ－２Ｒ均显著增高，与正常对照比较，Ｐ＜０００１。急性、亚急性重型及慢性重型乙型肝炎患者的ＣＤ＋４明显降低，ＣＤ＋８则显著升高，与对照组比较，Ｐ均＜００１。检测证实ｓＩＬ－２Ｒ增高与活化的ＣＤ＋８具有相关性，表明活化的ＣＤ＋８细胞主要是细胞毒性Ｔ细胞（ＣＴＬ），其在急性和亚急性重型肝炎发病中可能起重要作用。ＣＤ＋４、ＣＤ＋８细胞在急性和慢性重型乙肝中表达的不同，提示二者发病机制不同。     

Suppression by Trypanosoma brucei rhodesiense of the capacities of human T lymphocytes to express interleukin-2 receptors and proliferate after mitogenic stimulation.

We studied the suppressive effects induced in phytohemagglutinin (PHA)-stimulated human peripheral blood mononuclear cells (PBMC) by purified blood forms of Trypanosoma brucei rhodesiense. The parasite was found to markedly impair lymphocyte proliferation (measured in terms of [3H]thymidine incorporation). The extent of this effect increased with parasite concentration and was not due to mitogen absorption, depletion of medium nutrients, or PBMC killing by the parasite. Significant reductions in interleukin-2 receptor (IL-2R) expression, determined by flow cytometric analysis, were also observed in PHA-stimulated PBMC cultured in the presence of T. b. rhodesiense as evidenced by marked decreases in the surface density of the receptor. Concomitant decreases in the percentage of IL-2R+ cells were recorded in approximately half of the experiments. A discrete, dimly stained subpopulation of IL-2R+ cells were consistently demonstrable whether or not a reduction in the percentage of IL-2R+ cells occurred. Living, but not glutaraldehyde-fixed, parasites suppressed IL-2R expression. In kinetic studies, a low but reproducible level of suppression of IL-2R was demonstrable as early as 6 h after PHA stimulation; the extent of this effect became considerably more pronounced as additional culture time elapsed. Levels of IL-2 biological activity in cocultures of T. b. rhodesiense with PHA-stimulated PBMC were comparable with or higher than those present in control cultures lacking the parasite. Therefore, insufficient levels of this cytokine would be an unlikely explanation for the noted suppression of IL-2R expression and lymphoproliferation. These effects of T. b. rhodesiense could represent an important component of the mechanism by which immunosuppression develops in African sleeping sickness.     

Interleukin-2 augmentation of interleukin-1 and prostaglandin E2 production

Some of the major side effects of interleukin-2 (IL-2) therapy in the treatment of malignancies may be related to increased interleukin-1 (IL-1) and/or prostaglandin E2 (PGE2) production. We examined the effect of recombinant (rIL-2) on the in vitro production of IL-1 beta and PGE2 by unstimulated and LPS-activated human blood mononuclear cells (PBMC). We also compared the effect of rIL-2 on IL-1 beta production by adherent and nonadherent blood mononuclear cell populations. Cultures of PBMC (5 x 10(6)/ml) were incubated for 24 hr in media only (control, 1,000 U/ml rIL-2, 2 micrograms/ml LPS, or both LPS and rIL-2. Supernatants obtained from these cultures were analyzed for levels of IL-1 beta and PGE2 by radioimmunoassays. The addition of rIL-2 caused an increase in IL-1 beta production in 13 of 13 control PBMC cultures and in 11 of 13 LPS-stimulated cultures, which were significant increases as determined by paired t tests. When PBMC were fractionated into plastic adherent and nonadherent populations, the rIL-2 induced increases in IL-1 beta production were more consistent in control (six of seven cases) and LPS (seven of seven cases) cultures of plastic nonadherent cells than in control (three of seven cases) and LPS (four of seven cases) cultures of plastic adherent cells. Recombinant IL-2 did not increase PGE2 production in control PBMC cultures (none of four cases), but did so in LPS-stimulated PBMC cultures (three of four cases]. These results suggest that rIL-2 may increase IL-1 production in vivo and thus possibly account for some of the side effects of this therapy.     

慢性丙型肝炎患者抗病毒治疗前PBMC细胞因子的研究

目的 研究准备抗病毒治疗的慢性丙型肝炎患者的免疫特点.方法 将30例慢性丙型肝炎患者和10例正常对照外周血单个核细胞(PBMC)体外培养72 h后,用ELISA法检测培养上清中细胞因子IL-2、IL-4、IL-10、IL-12、IFN-γ和TNF-α的浓度.结果 (1)慢性丙型肝炎患者PBMC培养上清中IFN-γ、IL-10和TNF-α的水平明显升高(P＜0.05),没有检测到IL-2、IL-4、IL-12的基础分泌.(2)不同病情患者间的细胞因子的分泌水平差异无统计学意义(P＞0.05).结论 慢性丙型肝炎患者体内TH2型细胞因子的分泌占优势.提示通过调整TH1/TH2失衡可能达到抗病毒治疗目的.     

The profiles of interleukin (IL)-2, IL-6, and interferon-gamma production by peripheral blood mononuclear cells from house-dust-mite-allergic patients: a role for IL-6 in allergic disease

We have developed a model to measure cytokine production by peripheral blood mononuclear cells (PBMC) in vitro. In this report, we examine the production of interleukin-2 (IL-2), IL-6, and interferon-gamma (IFN-γ) by PBMC of house-dust-mite ( Dermatophagoides pteronyssinus )-allergic subjects. When stimulated with specific allergen ( D. pteronyssinus ), PBMC of patients produced significant levels of IL-2 and high levels of IL-6, but little or no IFN-γ. Nonatopic control PBMC also produced IL-6, although at lower levels, but no IL-2 or IFN-γ. A ubiquitous antigen, streptokinase/streptodornase (SKSD), induced high levels of IL-2 in patients, but only low levels of IFN-γ and IL-6. Nonatopic controls produced similar levels of IL-2 and IL-6, but high levels of IFN-γ to SKSD. IL-2 and IFN-γ levels induced by the T-cell mitogen phytohaemagglutinin (PHA) were similar in patient and control groups, but IL-6 levels were significantly lower in the patients. IgE synthesis in vitro was shown only in atopic PBMC cultures stimulated with specific allergen. The major points can be summarized as 1) IL-2 production by atopic patients in response to allergen; 2) IL-6 production to allergen by both atopic and nonatopic patients, but significantly increased in atopic patients; and 3) defective IFN-γ production by atopic patients to both allergen and antigen. These findings suggest that IL-6 may be important in the immune response to inhalent allergens such as D. pteronyssinus , possibly by creating a cytokine environment favourable to a T^H2 response, and that atopic patients exhibit a generalized defect of IFN-γ production, not related to the response to allergen.     

Prothymosin alpha enhances interleukin 2 receptor expression in normal human T-lymphocytes.

We investigated whether the enhancement, by prothymosin alpha (Pro alpha), of the phytohaemagglutinin-stimulated proliferation of human peripheral blood mononuclear cells (PBMC) is due to its affect on the number of cells expressing the interleukin 2 receptor (IL-2R) or the surface density of IL-2R on PBMC. Peripheral blood mononuclear cells were obtained from 21 donors. For both an optimal phytohaemagglutinin (PHA) concentration (H) and a 10-fold dilution (L), their responses fell in two classes, high (h) and low (l), making four dose--response situations. Pro alpha significantly increased the number and IL-2R density of cells expressing IL-2R only when the response in its absence was about half maximal, i.e. for PBMC responding well to the low PHA stimulus (group Lh) or PBMC responding poorly to the optimal stimulus (group Hl). The enhancement of IL-2R expression in group Lh by Pro alpha was dose-dependent and paralleled by increased proliferative response. It appears not to be mediated by IL-2, since it was unaffected when IL-2 production was suppressed by cyclosporin A. The early interaction of Pro alpha with lymphocytes did not require the presence of macrophages, but macrophages were necessary during lymphocyte activation for modulation of PHA-stimulated IL-2R expression to be affected. The immunoregulatory activity of Pro alpha may prove useful for improving the decreased T-cell function associated with immunodeficiency, or for restoration of normal IL-2R expression by the lymphocytes of aged individuals.     

小儿慢性丙型肝炎外周血T细胞亚群和TH1/TH2型细胞因子的研究

目的通过研究小儿慢性丙型肝炎外周血T细胞亚群及TH1/TH2型细胞因子的表达,进一步探讨小儿慢性丙型肝炎的免疫发病机制。方法(1)流式细胞仪(FACS)检测16例慢性丙型肝炎患儿及10例正常对照外周血T细胞亚群。(2)将慢性丙型肝炎患儿和正常对照外周血单个核细胞(PBMC)体外培养72h后,用ELISA法检测培养上清中TH1型细胞因子(IFN-γ、IL-2、IL-12和TNF-γ)和TH2型细胞因子(IL-4、IL-10)的浓度。结果(1)CD4 细胞无明显变化。CD8 细胞与正常对照比较明显升高(P<0.05)。CD3 细胞升高,CD4 /CD8 比值下降,但与正常对照比较无统计学意义(P>0.05)。(2)PBMC培养上清中IFN-γ、IL-10和TNF-α的水平明显升高(P<0.01),而没有检测到IL-2、IL-4、IL-12的基础分泌。结论慢性丙型肝炎患儿体内T淋巴细胞存在数量和功能的异常,CD8 细胞数升高,CD4 细胞功能异常,表现在以TH2型细胞因子的分泌为主。这可能与丙肝病毒(HCV)感染的慢性化有关。     

The role of interleukin 2 (IL-2) and serum-soluble IL-2 receptor cells in idiopathic IgA nephropathy.

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.     

Lactate dehydrogenase (LDH) isoenzymes and proliferative activity of lymphoid cells--an immunocytochemical study.

The regulation of cytokine production and T cell proliferation by other cytokines is mandatory in mediating inflammatory responses but the full understanding is far from complete. We have previously reported increased production of IL-2 and IL-2 receptors (IL-2R) in IgA nephropathy. The present study was undertaken to examine other cytokine production during T cell activation in IgA nephropathy. Peripheral blood mononuclear cells (PBMC) from 17 IgA nephritic patients and 14 controls were cultured with phytohaemagglutinin and phorbol myristate acetate for 48 h for maximal cytokine production. IL-2Rs and IL-4 receptors (IL-4Rs) expressed on cultured PBMC were studied by a radioimmunoassay using monoclonal antibodies against these receptors. Although the total cellular IL-2R expression and percentages of T helper and T suppressor cells did not differ between the patients and controls, there was a significant increase in activated T helper cells expressing IL-2R in patients with IgA nephropathy. The total cellular IL-4R expression was elevated in IgA nephritic patients (P less than 0.005). IL-2 production by PBMC was raised in IgA nephritic patients compared with controls (P less than 0.05) but no difference in IL-4 or IL-6 production was observed. The interferon-gamma production by PBMC was significantly increased in patients with IgA nephropathy (P less than 0.025). No correlation was observed between individual cytokine levels. Our data suggest there are selective increases in cytokine production in IgA nephropathy.     

Modulation of cell-bound and soluble CD23, spontaneous and ongoing IgE synthesis of human peripheral blood mononuclear cells by soluble IL-4 receptors and the partial antagonistic IL-4 mutant protein IL-4 (Y124D).

We studied the influence of human recombinant soluble interleukin-4 receptors (sIL-4R) and a partial antagonistic mutant IL-4 protein, IL-4(Y124D), on the in vitro CD23 expression, soluble (s)CD23 release and IgE synthesis of human peripheral blood mononuclear cells (PBMC). The data show that sIL-4R suppressed the IL-4-induced IgE synthesis of PBMC. sIL-4R fusion protein stabilized with human Fc gamma fragments showed a more pronounced effect than unconjugated sIL-4R. IL-4(Y124D) also suppressed the IL-4-induced IgE synthesis. The IL-4-induced antigen CD23 and its soluble fragments were suppressed by sIL-4R and IL-4(Y124D). PBMC of atopic donors with a spontaneous in vitro IgE synthesis showed a partial suppression of the IgE production after sIL-4R or IL-4(Y124D) application. The IgE synthesis and sCD23 release of normal donor PBMC were suppressed when the substances were applied 0-4 days after IL-4 treatment. After 4 days of IL-4 stimulation, sIL-4R and IL-4(Y124D) enhanced the IgE synthesis. These data demonstrate that sIL-4R and IL-4(Y124D) are suppressive for the primary IgE synthesis induced by IL-4. In contrast, the ongoing IgE synthesis was only partially modulated by sIL-4R and IL-4(Y124D), and in some conditions even an enhancement of the IgE production was observed. These data suggest a differential function for IL-4 in the early and late phase of PBMC IgE production.