再生障碍性贫血患者免疫调节剂治疗前后TNF和IL—2水平变化…

为了探讨再生障碍性贫血的免疫发病机理及抗Ｔ淋巴细胞单克隆抗体的免疫调节治疗作用，采用放射免疫分析法检测３０例ＡＡ患者ＭｃＡｂ－Ｔ治疗前后血清肿瘤坏死因子和白细胞介素－２水平及其中１０例ＡＡ外周血单个核细胞体外诱生ＴＮＦ和ＩＬ－２水平的变化。结果表明，治疗前ＡＡ患者血清ＴＮＦ水平显著增高，ＰＢＭＮＣ诱生的ＴＮＦ和ＩＬ－２水平均明显高于正常对照。     

羧甲基茯苓多糖对HPBL分泌IL—2,TNF,IL—6,IFN—γ的调节作用

用ＣＭＰ培养外周血淋巴细胞（ＨＰＢＬ）２４、３６、４８、７２ｈ采样检测的ＩＬ－２、ＴＮＦ、ＩＬ－６、ＩＦＮ－γ效价分别可达１３．６±４．３，４１．９±２．０，１８３７．４±４６４．３，１０３７．９±２１１．０Ｕ／ｍｌ，分别比无ＣＭＰ的细胞培养对照组的效价高０．８，７．４，０．５，１０．９倍（Ｐ＜０．０１），说明ＣＭＰ具有ＩＬ－２、ＴＮＦ、ＩＬ－６、ＩＦＮ－γ的诱生剂功能。由ＣＭＰ预处理ＨＰＢＬ后经ＰＨＡ和／或ＣｏｎＡ促诱生组的ＩＬ－２、ＴＮＦ、ＩＬ－６、ＩＦＮ－γ效价分别比无ＣＭＰ的ＰＨＡ和／或ＣｏｎＡ刺激的相应常规诱生组高１．２～２．８，０．５～１．１、０．５～０．８、０．４～０．６倍（Ｐ＜０．０１），尤以ＣＭＰ＋ＰＨＡ＋ＣｏｎＡ促诱生细胞因子效果最佳（Ｐ＜０．０１），说明ＣＭＰ又具有ＩＬ－２、ＴＮＦ、ＩＬ－６、ＩＦＮ－γ促诱生效应。     

抗T细胞单克隆抗体对再生障碍性贫血患者TNF和IL—2水平的影响

为探讨抗Ｔ淋巴细胞克隆抗体对再生障碍性贫血患者免疫功能的调节作用，采用放射免疫检测２５例ＡＡ患者ＭｃＡｂ－Ｔ治疗前后血清肿瘤坏死因子和白细胞介素－２（ＩＬ－２）水平及其中１０例周围血单个核细胞体外诱生ＴＮＦ和ＩＬ－２水平的变化。     

再生障碍性贫血患者细胞因子水平观察

为进一步探讨细胞免疫对ＡＡ发病的影响，阐明细胞因子在ＡＡ患者中变化的基础与临床意义，采用酶联免疫试剂盒ＥＬＩＳＡ法对３８例ＡＡ患者及２０例正常人外周血单个核细胞（ＰＢＭＮＣ）培养上清诱生Ｇ－ＣＳＦ，ＩＬ－６，ＴＮＦα，ＩＦＮα及ＩＬ－８水平进行测定，同时采用改良ＡＰＡＡＰ法观察外周血Ｔ细胞亚群及ＨＬＡ－ＤＲ抗原表达，结果ＡＡ患者ＰＢＭＮＣ培养上清中Ｇ－ＣＳＦ阳性率减低，ＩＬ－６，ＴＮＦαＩＦＮα及     

脑囊虫病患者外周血单个核细胞体外诱生IL—2,IFN—γ及 …

本文采用生物活性测定法检测了３１例脑囊虫病患者外周血单个核细胞（ＰＢＭＣ）体外诱生ＩＬ－２、ＩＦＮ－γ及ＴＮＦ－α活性，以３０例正常人作对照，探讨了脑囊虫病人在子的变化及在免疫调节中的作用。结果显示：脑囊虫病患者ＰＢＭＣ体外诱生的ＩＬ－２、ＩＦＮ－γ水平明显降低。与正常人相比差异显著（Ｐ〈０．０５，Ｐ〈０．０１），而患者ＰＢＭＣ体外诱生的ＴＮＦ－α水平明显高于正常对照组（Ｐ〈０．０１）；提示脑囊虫     

鼻咽癌患者外周血Th1细胞的变化及其与病程的关系

利用细胞因子诱生及ＥＬＩＳＡ等技术，研究了３８例不同分期的鼻咽癌（ＮＰＣ）患者、２３例正常人外周血单个核细胞（ＰＢＭＣ）分泌的细胞因子模式，较系统地研究了ＣＤ４＾＋Ｔ淋巴细胞亚群Ｔｈ１和Ｔｈ２所分泌的代表性的细胞因子类型ＩＬ－２、ＩＦＮ－γ，ＩＬ－４，ＩＬ－６，ＩＬ－１０等的变化，同时检测了ＮＰＣ患者血清中ＩＬ－２和ＩＬ－４水平。发现ＮＰＣ患者ＰＢＭＣ体外分泌ＩＬ－２的水平下降，ＩＬ－４的水平增高     

脑囊虫病患者外周血单个核细胞体外诱生IL-2、IFN-γ及TNF-α活性的研究

本文采用生物活性测定法检测了３１例脑囊虫病患者外周血单个核细胞（ＰＢＭＣ）体外诱生ＩＬ－２、ＩＦＮ－γ及ＴＮＦ－α活性，以３０例正常人作对照，探讨了脑囊虫病人细胞因子的变化及在免疫调节中的作用。结果显示：脑囊虫病患者ＰＢＭＣ体外诱生的ＩＬ－２、ＩＦＮ－γ水平明显降低，与正常人相比差异显著（Ｐ＜０．０５，Ｐ＜０．０１），而患者ＰＢＭＣ体外诱生的ＴＮＦ－α水平明显高于正常对照组（Ｐ＜０．０１）；提示脑囊虫病患者的ＣＤ＋４Ｔｈ１细胞呈低应答状态，脑囊虫病患者过量产生的ＴＮＦ－α可能是造成脑囊虫病的免疫病理损害原因之一。     

CMP促诱生IL—2,TNF—α,IL—6,IFNγ／α效应和产品中试

用羧甲基茯苓多糖（ＣＭＰ）预处理人外周血淋巴细胞（ＨＰＢＬ），在以ＰＨＡ和ＣｏｎＡ为主的复合诱生剂诱导培养２４、３６、４８、７２ｈ采样检测的促诱生组ＴＮＦ－α、ＩＬ－２、ＩＬ－６、ＩＦＮγ效价（ｘ±ｓ）分别为４５６．１±２４．２，４７５．６±１８５．７，７４３３±１１８９．９，５５８３．０±５３５．５ＩＵ／ｍｌ，分别比无ＣＭＰ的常规诱生组效价高１．５，３．８，１．８，１．４倍；在以ＮＤＶ－Ｆ病毒为诱生剂诱导培养２２ｈ采样，并经酸化和中性化后检测的ＩＦＮ－α效价可达２１２７４．２±５５２３．０ＩＵ／ｍｌ，比无ＣＭＰ的常规诱生组高１．２倍，均有显著差异（Ｐ＜０．０１），说明ＣＭＰ对上述五种细胞因子均有明显的促诱生效应。此外，还采用ＣＭＰ促诱生技术，对ＴＮＦ－α、ＩＬ－２、ＩＬ－６、ＩＦＮγ和ＩＦＮ－α细胞因子进行了中试，提出了低成本、高效益的中试工艺路线，有待于在制备天然细胞因子的细胞工程中推广应用     

阿米巴肝脓肿患者血清细胞因子水平与免疫防卫能力的研究

目的 了解阿米巴肝脓肿患者抗体的免疫防卫能力。方法 ＥＬＩＳＡ、比色法及流式细胞仪等检测了４０例阿米巴肝脓肿患者血清细胞因子ＴＮＦ－α,ＩＬ－６,ＩＬ－８,ｓＩＬ－２Ｒ,弓形虫感染率,ＮＯ,血液ＣＤ４／ＣＤ８Ｔ细胞,红细胞Ｃ３ｂ受体花环率（ＲＢＣ－Ｃ３ｂＲＲ）及免疫复合物花环率（ＲＢＣ－ＩＣＲ）。结果 ＴＮＦα,ＩＬ－,ＩＬ－８,ｓＩＬ－２Ｒ,ＮＯ,ＲＢＣ－ＴＣＲ显著高于正常对照组,ＲＢＣ－Ｃ３ｂ     

重型乙型肝炎患者TNF和IL－1的检测及意义

检测３０例重型乙型病毒性肝炎（重型肝炎）患者血清和外周血单个核细胞（ＰＢＭＣ）培养上清中肿瘤坏死因子（ＴＮＦ）水平及ＰＢＭＣ诱生的白细胞介素１（ＩＬ－１）活性，结果：重型肝炎患者ＴＮＰ和ＩＬ－１水平均增高，且二者呈正相关。提示ＴＮＦ和ＩＬ－１在重型肝炎的发病机制中起重要作用。     

再生障碍性贫血患者免疫调节剂治疗前后TNF和IL-2水平变化及意义

为了探讨再生障碍性贫血(AA)的免疫发病机理及抗T淋巴细胞单克隆抗体(McAb-T)的免疫调节治疗作用,采用放射免疫分析法检测30例AA患者McAb-T治疗前后血清肿瘤坏死因子(TNF)和白细胞介素-2(IL-2)水平及其中10例AA外周血单个核细胞(PBMNC)体外诱生TNF和IL-2水平的变化。结果表明,治疗前AA患者血清TNF水平显著增高(p<0.01),PBMNC诱生的TNF和IL-2水平均明显高于正常对照(p<0.01)。治疗后血清TNF和PBMNC诱生的TNF和IL-2水平降低,与对照组比较无显著差异(p>0.05)。提示AA患者存在造血调控因子分泌异常,McAb-T对TNF和IL-2能发挥特异性的免疫调节作用。     

再生障碍性贫血患者细胞免疫指标的观察

采用酶免疫和放射免疫法分析了再生障碍性贫血(AA)患者外周血T淋巴细胞亚群、血清肿瘤坏死因子(TNF)、γ-干扰素(IFN-γ)和IL-2水平,以及患者外周血单个核细胞体外诱生的上述细胞因子水平。结果表明:患者CD4/CD8细胞比值降低或倒置(P<0.001),血清TNF和IFN-γ水平显著增高(P<0.01),外周血单个核细胞诱生的TNF、IFN-γ和IL-2水平均明显高于正常对照(P<0.01)。提示T淋巴细胞亚群比例失调和TNF、IFN-γ等造血负调控因子的过量分泌可能与AA的发病机制有关。     

小儿急性肾炎患者IL-2、IL-6、TNF水平的变化

目的:探讨了小儿急性肾炎患者血清白介素-2(IL-2)、白介素-6(IL-6)、肿瘤坏死因子(TNF)在急性肾炎发生、发展过程中的变化及相互关系。方法:用放射免疫分析检测了31例急性肾炎患儿血清中IL-2、IL-6、TNF水平,并以30例正常健康儿童作比较。结果:急性肾炎患儿血清中IL-6、TNF水平显著高于正常人组(P<0.01),而IL-2水平显著低于正常人组(P<0.01)。直线相关分析显示,IL-6、TNF水平与BUN呈正相关(P<0.01)。结论:血清IL-2、IL-6、TNF在小儿急性肾炎的发生、发展过程中相互作用,观察其浓度的变化对探讨其发病机理及指导用药均有重要临床价值。     

糖尿病肾病患者与相关细胞因子水平的变化

目的:探讨了糖尿病肾病患者的血清白介素-2、白介素-6、白介素-8和肿瘤坏死因子水平的变化在肾病发生、发展过程中的作用。方法:应用放射免疫分析对38例糖尿病肾病患者和36例正常人进行了血清IL-2、IL-6、IL-8和TNF水平的检测。结果:糖尿病肾病患者血清中IL-6、IL-8和TNF水平非常显著地高于正常人组(P<0.01),而IL-2水平则显著地低于正常人组(P<0.01)。结论:血清IL-2、IL-6、IL-8和TNF水平的变化在糖尿病肾病的发生和发展中相互作用,观察其浓度的变化对探讨其发病机理、预防和指导用药均有十分重要的临床价值。     

Graves病患者血清细胞因子水平和甲状腺功能指标的检测分析

目的:探讨弥漫性毒性甲状腺肿(GravesDisease,GD)对人体血清白细胞介素-2(IL-2)、白细胞介素-8(IL-8)、肿瘤坏死因子(TNF)水平的影响。方法:采用放射免疫技术,检测135例GD患者治疗前后的IL-2、IL-8、TNF水平。结果:GD治疗前IL-2水平均低于治疗后和正常对照组,而IL-8、TNF水平在治疗后降低,且组间比较具有显著性意义(P<0.01)。对GD未治疗组血清中IL-2、IL-8、TNF与FT3、FT4、TSH进行相关性分析,结果显示IL-2与FT3、FT4呈显著负相关(P均<0.01);IL-8、TNF与FT3、FT4、TSH均无相关性(P均>0.05)。结论:IL-2、IL-8、TNF参与GD的发生与发展过程,与GD的免疫紊乱与功能状态异常间存在十分重要的内在联系。     

山莨菪碱预处置对大鼠ARDS血清及肺组织中细胞因子的影响

目的 观察山莨菪碱(654-2)预处置对大鼠油酸型急性呼吸窘迫综合征(ARDS)血清及肺组织中IL-6、IL-8、TNF-α及IL-10的影响,探讨654-2治疗ARDS的理论基础。方法 经舌下静脉注射油酸复制大鼠ARDS模型,用酶联免疫吸附试验测定血清及肺组织匀浆上清液中IL-6、IL-8、TNF-α和IL-10水平。结果 ARDS组大鼠血清IL-6、TNF-α、IL-10含量和肺组织匀浆上清液中IL-6、IL-10含量明显高于对照组(P<0.01或0.05)。654-2预处置组血清和肺组织中IL-10水平显著高于对照组(P<0.01或0.05)。654-2预处置组血清和肺组织中IL-6、TNF-α含量明显低于ARDS组(P<0.01或0.05),而IL-8和IL-10含量两者无显著性差异。结论 IL-6、IL-8、TNF-α及IL-10在大鼠油酸型ARDS炎症过程中可能起重要作用,654-2可能通过抑制IL-6、TNF-α过度分泌而减轻肺损伤。     

Pemphigus vulgaris: the role of IL-1 and IL-1 receptor antagonist in pathogenesis and effects of intravenous immunoglobulin on their production

Intravenous immunoglobulin (IVIG) is increasingly being used for the treatment of autoimmune diseases. In the present report, the role of IVIG on in vivo and in vitro production of IL-1 and IL-1 receptor antagonist (Ra) was studied in patients with pemphigus vulgaris (PV). Serum samples from 20 untreated patients with active PV prior to initiation of systemic therapy, 20 patients receiving IVIG treatment, 20 patients in clinical remission after conventional therapy, and 20 normal human controls were studied to determine the serum levels of IL-1alpha, IL-1beta, and IL-1Ra. The in vitro production of these cytokines was measured in the culture supernatant of peripheral blood mononuclear cells (PBMC) from 10 PV patients immediately before and after IVIG therapy and from age and sex-matched 10 healthy donors simultaneously. Elevated levels of IL-1alpha and IL-1beta were detected (i) in the serum of untreated PV patients with active disease prior to systemic therapy and (ii) before IVIG infusions in patients receiving IVIG therapy. These increased levels are statistically significant when compared to the levels in healthy controls (P < 0.01). A marked reduction of IL-1alpha and IL-1beta was detected (i) in the serum of patients in prolonged clinical remission and (ii) immediately after IVIG infusion in those patients on IVIG therapy. Increased level of IL-1Ra was detected in PV patients in prolonged clinical remission and after IVIG infusion in those receiving IVIG therapy. These differences were statistically significant when compared to the levels in normal controls and to the levels in the sera of patients with active disease (P < 0.01) or just before the beginning of IVIG infusion (P < 0.01). Similar differences in the levels of IL-1alpha, IL-1beta, and IL-1Ra were found in the culture supernatant of PBMC isolated from the PV patients pre and post IVIG therapy. These observations suggests that, compared to normal controls, patients with active PV have reversed levels of IL-1alpha, IL-1beta, and IL-1Ra. IVIG therapy may down-regulate production of IL-1alpha and IL-1beta and enhance production of IL-1Ra, in vivo and in vitro. This might be one of the important mechanisms by which IVIG produces its early therapeutic effects in pemphigus vulgaris.     

The in vivo effects of tumour necrosis factor blockade on the early cell mediated immune events and syndrome expression in rat adjuvant arthritis

Anti-TNF therapy is effective in rheumatoid arthritis (RA); however, its mechanisms of action are incompletely understood. T cell-driven mechanisms are thought to play an important role in RA and the effects of TNF blockade on these mechanisms are unclear. Adjuvant arthritis (AA) is a T cell dependent model of inflammatory arthritis. The aims of this study were to investigate the effects of TNF blockade on in vivo T cell cytokine expression and to clarify the role of TNF in the inguinal lymph nodes (ILN) in early arthritis. AA was induced in male DA rats. Rats received either 3 mg/kg or 10 mg/kg PEG sTNF-RI at days 0, 2 and 4 postinduction or 10 mg/kg anti-TNF antibody on day of arthritis induction. Control rats received either saline or normal sheep serum. Paw volume was assessed every 3-4 days. Rats were sacrificed on days 0, 6, 13 and 21 postinduction. Ankles were removed for quantitative radiology and histology. Synovium and ILN were removed for cell culture and to determine mRNA expression of cytokines using semiquantitative RT-PCR. TNF and IFN-gamma protein production was measured using a bioassay and an ELISA. TNF blockade did not suppress mRNA expression of T cell cytokines in the ILN of rats in the early phase of AA, suggesting ongoing T cell activity. TNF protein production by ILN cells in culture was reduced in PEG sTNF-RI treated rats, although mRNA expression was increased in the ILN prior to culture. Early administration of PEG sTNF-RI did not attenuate AA, in contrast to an anti-TNF antibody, which suppressed disease. A shorter half-life for the PEG sTNF-RI compared with the anti-TNF antibody or the development of anti-PEG sTNF-RI antibodies may account for these results.     

Tumour necrosis factor-alpha (TNF), lymphotoxin and TNF receptor levels in serum from patients with Wegener's granulomatosis

Wegener's granulomatosis (WG) is a systemic inflammatory disease with vasculitis as the key feature. Abnormal expression of tumour necrosis factor alpha (TNFalpha) is considered of prime pathogenic importance in several inflammatory diseases. The effects of TNFa are mediated by TNF receptors (TNF-R), and these receptors are often found in soluble forms (sTNF-R), which can modulate TNFalpha actions. To evaluate the clinical importance of the TNF family of cytokines, the serum levels of TNFalpha, TNFbeta, now termed lymphotoxin (LTalpha), and sTNF-R1 and sTNF-R2 were measured by ELISA in 8 patients with WG during active disease and during immunosuppressive treatment, and in 11 healthy controls in parallel. Serum concentrations of TNFalpha were undetectable in all except two controls (18%) and three patients with WG (37%). After 7 days of therapy, six of the WG patients had measurable TNFalpha levels. Examination of the relative amounts of TNFalpha and sTNF-R indicated that TNFalpha was mostly bound to its soluble receptors. In WG, the serum levels of sTNF-R1 and sTNF-R2 were dramatically increased (p<0.01), with little or no variation during treatment. While the IL-1beta levels did not deviate significantly from controls, the IL-1ra levels were significantly elevated in the WG patients throughout the study period (p<0.01).