雷公藤多甙与DC单抗对小鼠自身免疫性甲状腺炎作用的研究

在建立小鼠自免疫性甲状腺炎的基础上,研究雷公藤多甙和树突状细胞单克隆抗体对诱导小鼠ＡＩＴ的影响。结果表明,经雷公藤多甙,ＤＣ单抗单独及联合应用,与未用药组相比,血清中ＴｇＡｂ水平、Ｔｇ刺的淋巴细胞的增殖能力、脾淋巴细胞产生ＴＮＦ水平无显著降低,其中以联合应用组尤为明显,病理学检查亦之相符。     

HCMV感染对单核细胞HLA－DR表达的影响

本文采用细胞ＥＬＩＳＡ法，研究发现人巨细胞病毒（ＨＣＭＶ）感染对单核细胞ＨＬＡ－ＤＲ的影响。结果表明ＨＣＭＶ感染后１ｄ，单核细胞ＨＬＡ－ＤＲ表达显著增高（Ｐ＜０．０１），以后逐渐降低，ｄ５降至对照水平；ＩＦＮγ（５００Ｕ／ｍｌ）．ＴＮＦ（２５０Ｕ／ｍｌ）、ＩＬ－６（５００／ｍｌ）、ＩＬ－１（５００／ｍｌ）均能不同程度地刺激单核细胞ＨＬＡ－ＤＲ表达；ＨＣＭＶ感染后，细胞因子刺激ＨＬＡ－ＤＲ表达的水平在感染后ｄ５，较对照组均显著降低（Ｐ＜０．０１）；ＩＬ－１＋ＩＦＮ－γ及ＴＮＦ＋ＩＦＮ－γ在刺激单核细胞ＨＬＡ－ＤＲ表达时有协同作用；ＨＣＭＶ感染后，ＩＦＮ－γ＋ＩＬ－１及ＴＮＦ＋ＩＦＮ协同刺激单核细胞ＨＬＡ－ＤＲ表达水平较对照组显著降低（Ｐ＜０．０１）。结果提示：在ＨＣＭＶ感染引起免疫抑制过程中，其引起单核细胞ＨＬＡ－ＤＲ表达降低是一重要机制。     

HCMV感染对单核细胞HLA－DR表达的影响

本文采用细胞ＥＬＩＳＡ法，研究发现人巨细胞病毒（ＨＣＭＶ）感染对单核细胞ＨＬＡ－ＤＲ的影响。结果表明ＨＣＭＶ感染后１ｄ，单核细胞ＨＬＡ－ＤＲ表达显著增高（Ｐ＜０．０１），以后逐渐降低，ｄ５降至对照水平；ＩＦＮγ（５００Ｕ／ｍｌ）．ＴＮＦ（２５０Ｕ／ｍｌ）、ＩＬ－６（５００／ｍｌ）、ＩＬ－１（５００／ｍｌ）均能不同程度地刺激单核细胞ＨＬＡ－ＤＲ表达；ＨＣＭＶ感染后，细胞因子刺激ＨＬＡ－ＤＲ表达的水平在感染后ｄ５，较对照组均显著降低（Ｐ＜０．０１）；ＩＬ－１＋ＩＦＮ－γ及ＴＮＦ＋ＩＦＮ－γ在刺激单核细胞ＨＬＡ－ＤＲ表达时有协同作用；ＨＣＭＶ感染后，ＩＦＮ－γ＋ＩＬ－１及ＴＮＦ＋ＩＦＮ协同刺激单核细胞ＨＬＡ－ＤＲ表达水平较对照组显著降低（Ｐ＜０．０１）。结果提示：在ＨＣＭＶ感染引起免疫抑制过程中，其引起单核细胞ＨＬＡ－ＤＲ表达降低是一重要机制。     

白细胞介素6在Graves病的发病及骨代谢中的作用

采用白细胞介素 ６依赖性细胞株ＭＨ６０· ＢＳＦ增殖反应ＭＴＴ法，测定了 ５３例 Ｇｒａｖｅｓ病（ＧＤ）患者外周血单个核细胞（ＰＢＭＣ）培养上清中ＩＬ－６水平。结果未治疗组、治疗未缓解 组 ＩＬ－６水平高于缓解组和对照组（Ｐ＜ ０． ０１），后两者间无差异（Ｐ＞ ０． ０５），ＩＬ－６与血清游离三 碘甲状腺原氨酸（ＦＴ３）、游离甲状腺素（ＦＴ４）、甲状腺微粒体抗体（ＴｍＡｂ）、甲状腺球蛋白抗体 （ＴｇＡｂ）、骨钙素（ＢＧＰ）呈正相关，与桡、尺骨密度均值（ＢＭＤ）呈负相关。提示ＩＬ－６在ＯＰ发病与骨 代谢中起作用。ＩＬ－６可作为ＧＤ患者治疗效果的判定和预后以及预防骨质疏松症（ＯＰ）发生的重要 指标。     

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水平显著曾高（Ｐ〈０．０１），ＰＢＭＮＣ诱生的ＴＮＦ和ＩＬ－２水平均明显高     

内皮细胞源性IL—8对人树突状细胞作用的研究

目的：探讨内皮源性白细胞介素－８（ＩＬ－８）对人树突状细胞（ＤＣ）的作用。方法：用ＴＮＦ－α分别诱导内皮细胞和单核细胞产生ＩＬ－８,并将这２种不同来源的ＩＬ－８分别加入ＤＣ常规诱导培养的早期（第３天）及后期（第７天）,培养至第９天收获细胞。采用流式细胞术（ＦＣＭ）分析ＤＣ的表型;体外混合淋巴细胞反应（ＭＬＲ）测定ＤＣ刺激Ｔ细胞增殖能力;ＥＬＩＳＡ检测培养上清中ＩＬ－１２的含量;ＰＩ染色观察ＤＣ凋亡。结果：在ＤＣ培养的早期（第３天）加入内皮源性ＩＬ－８可以抑制ＤＣ的成熟,ＦＣＭ分析表明：ＣＤ１ａ,ＣＤ４０,ＣＤ８０,ＣＤ８３,ＨＬＡ－ＤＲ等ＤＣ表面标志显著下降,而ＣＤ１４表达率明显高于常规培养组。同时,激发同种Ｔ细胞增殖的能力及分泌的ＩＬ－１２量均显著低于常规组（Ｐ〈０．０１）,而加入单核细胞来源的ＩＬ－８则无此     

腺病毒、合胞病毒对外周血单个核细胞的IL-2受体表达及TNFα产生的影响

近年来国内外均注意到细胞因子及受体与病毒感染的关系。作者用１００ＴＣＩＤ５０的７型腺病毒（ＡＤＶ）及呼吸道合胞病毒（ＲＳＶ）Ｌｏｎｇ株刺激正常人体外培养的外周血淋巴细胞（ＰＢＭＣ），ＡＰＡＡＰ法检测淋巴细胞ＩＬ－２受体阳性率，酶联免疫法检测淋巴细胞上清液的ＴＮＦａ。初步观察了ＡＤＶ、ＲＳＶ对人ＰＢＭＣ的ＩＬ－２受体表达、ＴＮＦα产生的影响。经２００Ｕｇ／ｍｌ的ＰＨＡ活化的ＰＢＭＣ加入ＡＤＶ、ＲＳＶ后对照组ＩＬ－２＋细胞百分率为３４．３％，ＡＤＶ组为１７．３％，ＲＳＶ组为１７％，较对照组均显著降低…     

皮质醇导致脓毒症大鼠TNF-α释放增加

目的：探讨皮质醇对脓毒症大鼠ＴＮＦ－α、ＩＬ－６释放的影响及其临床意义。方法：ＳＤ大鼠５８只,分为５组,Ａ、Ｃ组于盲肠结扎穿孔ＣＬＰ后每１２ｈ皮下注射氢化可的松（３０ｍｇ／ｋｇ）,Ｂ、Ｄ组于ＣＬＰ后同时点注等量生理盐水,Ｅ组为对照组。Ａ、Ｂ组于４８ｈ,Ｃ、Ｄ组于２４ｈ处死,测定血及腹水中ＴＮＦ－α、ＩＬ－６含量和血中皮质醇水平。结果：Ａ组死亡３例,余各组无死亡。Ａ组血浆皮质醇和ＴＮＦ含量均显著高于Ｂ、Ｃ、Ｄ、Ｅ组（Ｐ＜００５）。Ａ、Ｂ、Ｃ、Ｄ组腹腔液中ＴＮＦ－α含量显著高于Ｅ组（Ｐ＜００５）。所有大鼠腹腔液中ＴＮＦ－α、ＩＬ－６含量均显著高于血浆（Ｐ＜００５）。结论：脓毒症时,应用皮质醇可使血浆ＴＮＦ－α含量升高,且随作用时间延长ＴＮＦ－α升高愈显著,并伴有动物死亡率增加。但对血浆及腹腔液中ＩＬ－６含量无显著影响。     

秋水仙碱对单核细胞产生细胞因子的影响

微管聚合抑制剂秋水仙碱（Ｃｏｌ，１０－５ｍｏｌ／Ｌ）可抑制ＬＰＳ刺激人单核细胞分泌１７ｋＤＴＮＦ－α及膜相关２６ｋＤＴＮＦ－α；与之相反，它却可促进ＩＬ－１β（多为分泌型）的分泌，而对ＩＬ－１α（多为膜相关型）则表现为抑制作用。对于ＩＬ－６，Ｃｏｌ无明显影响。Ｎｏｒｔｈｅｒｎ分析显示，Ｃｏｌ对ＴＮＦ－α及ＩＬ－１βｍＲＮＡ产生亦表现为相反作用，即对前者抑制，对后者促进作用。     

雷公藤对哮喘豚鼠外周血淋巴细胞IL-5、粒细胞-巨噬细胞集落刺激因子mRNA及CD4+、CD8+表达的影响

目的：探讨哮喘豚鼠白介素－ ５（ＩＬ－ ５） 、粒细胞－ 巨噬细胞集落刺激因子（ ＧＭ － ＣＳＦ） 及ＣＤ４ ＋ 和ＣＤ８ ＋ Ｔ 细胞在哮喘发病中的作用及雷公藤的干预作用。方法：实验分为哮喘组、雷公藤治疗组（ 处理组） 和对照组,每组各１０ 只豚鼠,采用原位杂交方法检测豚鼠外周血淋巴细胞的ＩＬ－ ５ 、ＧＭ－ ＣＳＦ ｍ ＲＮＡ 表达;应用免疫细胞化学方法检测外周血淋巴细胞ＣＤ４ ＋ 和ＣＤ８ ＋ 的表达。结果：哮喘组外周血淋巴细胞ＩＬ－ ５ 、ＧＭ－ ＣＳＦ－ ｍ ＲＮＡ 表达均明显高于处理组和对照组（ Ｐ＜ ０－０１） ,而处理组和对照组无显著差异。哮喘组外周血淋巴细胞ＣＤ４ ＋ 表达明显高于对照组和处理组（ Ｐ＜０－０１） ,ＣＤ８ ＋ 表达低于对照组和处理组（ Ｐ＜ ０－０５） 。结论：哮喘豚鼠外周血淋巴细胞ＩＬ－ ５ 、ＧＭ － ＣＳＦ ｍ ＲＮＡ 表达增高、ＣＤ４ ＋ 表达增高,ＣＤ８ ＋ 表达降低,而雷公藤甲素可降低外周血淋巴细胞ＩＬ－ ５ 、ＧＭ － ＣＳＦ ｍＲＮＡ 表达,并可提高ＣＤ８ ＋ 表达,降低ＣＤ４ ＋ 表达。表明雷公藤可能在抗哮喘气道炎症中发挥一定作用     

No development of experimental autoimmune thyroiditis in nude mice.

Homozygeous nu/nu mice do not develop experimental autoimmune thyroiditis and circulating thyroglobulin autoantibodies after two immunizations with murine thyroid extract and fortified complete Freund's adjuvant. However, heterozygeous nu/+ mice are perfectly apt for the induction of both thyroiditis and thyroglobulin autoantibodies. These results provide further evidence for the assumption that the development of experimentally induced autoimmune thyroiditis depends on the presence of T-cells as opposed to the spontaneously occurring autoimmune thyroiditis in Obese strain (OS) chickens which is mediated by B-effector cells. The present data further show that thyroglobulin is a T-dependent antigen in the mouse.     

Thyroid hormones fail to influence experimental autoimmune thyroiditis

The effect of thyroid hormones on experimental autoimmune thyroiditis in the rat has been studied to determine whether the autoimmune process is influenced by alteration of thyroid hormone secretion from the diseased gland. Restoration of thyroid hormone levels in vivo had no effect on thyroglobulin antibody production or thyroiditis, and no effect of thyroid hormone on antibody secretion was found with in vitro culture of lymphocytes, suggesting that the pathogenesis of autoimmune thyroiditis is independent of thyroid hormone secretion.     

Adhesion molecule monoclonal antibodies inhibit experimental autoimmune thyroiditis.

To examine the role played by adhesion molecules in thyroid autoimmunity, we have assessed the effect of administering monoclonal antibodies (mAb) against intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen-1 (LFA-1) in experimental autoimmune thyroiditis, induced by immunizing rats with thyroglobulin in complete Freund's adjuvant. The antibody against LFA-1, but not against ICAM-1, reduced thyroglobulin antibody production (P < 0.01) and both antibodies caused a significant reduction (P < 0.002) in the severity of the thyroidal lymphocytic infiltration. In vitro, both mAb impaired the proliferative response of splenic and lymph node T cells to thyroglobulin, but only the antibody against LFA-1 reduced thyroid cell killing assessed using splenic lymphocytes as effectors. Monoclonal antibodies against both these adhesion molecules appear to inhibit cell-mediated autoimmunity in vivo, but only the LFA-1 mAb reduced the autoantibody response.     

Maturation of dendritic cells by necrotic thyrocytes facilitates induction of experimental autoimmune thyroiditis

Dendritic cell (DC) maturation is required for efficient presentation of autoantigens leading to autoimmunity. In this report, we have examined whether release of tissue antigens from necrotic thyroid epithelial cells can trigger DC maturation and initiation of a primary anti-self response. DC were cocultured with either viable (VT/DC) or necrotic (NT/DC) thyrocytes, and their phenotypic and functional maturation as well as immunopathogenic potential were assessed. Significant up-regulation of surface MHC class II and costimulatory molecule expression was observed in NT/DC but not in VT/DC. This was correlated with a functional maturation of NT/DC, determined by IL-12 secretion. Challenge of CBA/J mice with NT/DC, but not with VT/DC, elicited thyroglobulin (Tg)-specific IgG as well as Tg-specific CD4(+) T-cell responses and led to development of experimental autoimmune thyroiditis. These results support the view that thyroid epithelial cell necrosis may cause autoimmune thyroiditis via maturation of intrathyroidal DC.     

Influence of immunomodulators,niridazole and levamisole,on autoimmune murine thyroiditis

The pathogenesis of murine autoimmune thyroiditis, induced in mice by immunization with mouse thyroglobulin emulsified in Freund's complete adjuvant, is unclear. To investigate the role of cell-mediated immunity in the murine thyroiditis, niridazole (100 mg/kg) and levamisole (12.5 mg/kg) were administered in mice before or after the antigenic challenge.Niridazole decreased the severity of thyroid infiltrates when started before the antigenic challenge. A similar inhibitory effect was observed after administration of levamisole. These findings are consistent with the possibility of a direct involvement of T-lymphocytes in the pathogenesis of autoimmune murine thyroiditis.     

亚硒酸钠对实验性自身免疫性甲状腺炎大鼠甲状腺细胞凋亡的影响

目的 探讨亚硒酸钠对实验性自身免疫性甲状腺炎(EAT)大鼠甲状腺细胞凋亡的影响.方法 Wistar大鼠分为正常对照组、自身免疫性甲状腺炎(EAT)组和硒干预EAT组.制备EAT大鼠模型,硒干预EAT组给予亚硒酸钠灌胃.用放射免疫法(RIA)测定各组大鼠自身抗体水平,HE染色观察甲状腺组织病理改变及TUNEL法标记甲状腺组织中凋亡细胞,观察甲状腺细胞凋亡情况.结果 正常对照组、EAT组、硒干预EAT组的TgAb分别(6.94±1.13)%、(36.24±3.64)%、(17.23±2.90)%,TmAb分别为(5.96±1.40)%、(27.12±5.06)%、(15.98±2.45)%.硒干预EAT组TgAb、TmAb水平较EAT组明显下降(P<0.05).各组大鼠甲状腺组织炎症程度及凋亡程度评分结果比较显示,不同组别的甲状腺组织病变程度间差别有显著性(P<0.001),硒干预EAT组的甲状腺滤泡破坏程度较EAT组减轻,淋巴细胞浸润减少(P<0.05),甲状腺细胞的凋亡数量较EAT组明显减少(P<0.05).结论 亚硒酸钠可能通过抑制甲状腺细胞的凋亡来减轻或抑制自身免疫性甲状腺炎的免疫损伤.     

Target organ susceptibility and autoantibody production in an animal model of spontaneous autoimmune thyroiditis.

F1-hybrids of Obese strain (OS) chickens, afflicted with spontaneous autoimmune thyroiditis (SAT), and normal, inbred CB chickens, do not develop severe thyroiditis. About 50% of these crosses show circulating autoantibodies to thyroglobulin (TgAAb), but the thyroid glands are only slightly infiltrated, suggesting that the target organ is not susceptible to autoimmune attack. In the present study we show that despite this mild infiltration TgAAb are only synthesized by lymphoid cells within the thyroid gland. Furthermore, we demonstrate that immunization with chicken thyroglobulin (Tg) in complete Freund's adjuvant causes severe experimental autoimmune thyroiditis (EAT) in F1(OSxCB) hybrids.     

Anti-CD44 treatment does not prevent the extravasation of autopathogenic T cells to the thyroid in experimental autoimmune thyroiditis

The hyaluronic acid binding glycoprotein CD44 is expressed on a wide variety of cells, and by mediating interactions between cells and extracellular matrices promotes the movement of cells from the circulation into organs. Recent reports have described the effects of an antibody specific for CD44 (IM7) that has beneficial effects in two murine models of autoimmune disease. Both experimental allergic encephalomyelitis (EAE) and collagen-induced arthritis were ameliorated by treatment with IM7, which was considered to be acting by preventing the homing of lymphocytes to the relevant inflammatory sites, namely the central nervous system and the synovium, respectively. In this study the same anti-CD44 antibody was used to try to prevent leucocytic infiltration of the thyroid in the murine model of Hashimoto's thyroiditis, experimental autoimmune thyroiditis (EAT). We report that, in contrast to the previous findings, this antibody had an exacerbating effect on thyroiditis induced by immunization of mice with mouse thyroglobulin (MTg) and complete Freund's adjuvant (CFA). Thyroid infiltrates lasted longer and showed increased severity compared with untreated or control antibody-treated mice. Antibody responses to MTg were unaffected by antibody treatment. The data suggest that simple rules cannot be drawn that predict the potential broad therapeutic use of anti-CD44 reagents, presumably due to differences in the cellular phenotypes and the dynamics of their movement into inflammatory sites during different disease processes.