自身免疫性甲状腺疾病与Th1/Th2细胞因子

自身免疫性甲状腺疾病（AITD）的发生与Th1/Th2细胞群的偏移有关，桥本氏甲状腺炎的发病常表现为Th1细胞因子水平高于Th2细胞因子水平，而Graves'病中Th2细胞因子占优势。深入研究Th1/Th2细胞群的偏移在AITD发病中的作用，有助于进一步阐明AITD的发生机理。     

自身免疫性甲状腺疾病患者甲状腺内Th1/Th2细胞失衡研究

目的　探讨甲状腺中Th1/Th2 细胞失衡在自身免疫性甲状腺疾病 (AITD)发病中的作用。方法　选取 13例Graves病 (GD)患者、12例桥本甲状腺炎 (HT)患者 ,并以 8例非毒性结节性甲状腺肿患者作为对照进行研究。采用免疫组化染色方法检测这些患者甲状腺内单个核细胞 (ITMC)的γ 干扰素(IFN γ)和白介素 4(IL 4)细胞因子抗原表达 (分别代表Th1,Th2 分泌的细胞因子 ) ,并与外周血甲状腺刺激性抗体 (TSAb)、甲状腺球蛋白抗体 (TGAb)、甲状腺微粒体抗体 (TMAb)等免疫学指标进行相关分析。结果　 ( 1)GD、HT患者ITMC的IL 4、IFN γ阳性表达明显高于对照组 (均P <0 .0 1) ;GD患者ITMC的IL 4阳性表达明显高于IFN γ阳性表达 ;而HT患者ITMC的IFN γ阳性表达则明显高于IL 4阳性表达(均P <0 .0 5 ) ;( 2 )GD患者ITMC的IL 4阳性表达与TSAb显著正相关 (r =0 .67,P <0 .0 1) ,ITMC的IFN γ阳性表达与TSAb无相关性 ;HT患者ITMC的IFN γ阳性表达与TGAb、TMAb均呈显著正相关(分别为r =0 .65 ,r =0 .5 9,均P <0 .0 5 ) ,但ITMC的IL 4阳性表达与TGAb、TMAb均无相关性。结论　GD患者Th1/Th2 细胞平衡失衡偏向以Th2 占优势的免疫应答 ,而HT患者Th1/Th2 平衡失衡偏向以Th1占优势的免疫应答。     

自身免疫性甲状腺疾病中Th1/Th2细胞平衡

辅助性T细胞(Th)可以根据其分泌的细胞因子而分为Th1和Th2两种不同的亚群,Th1/Th2失衡在自身免疫性甲状腺疾病的发病机制中起重要作用.Graves病可能以Th2型细胞因子介导的体液免疫为主,桥本甲状腺炎可能以Th1型细胞因子介导的细胞免疫为主,而Th1/Th2细胞因子共同参与Graves突眼的形成.     

自身免疫性甲状腺疾病中Thl／Th2细胞平衡

辅助性T细胞(Th)可以根据其分泌的细胞因子而分为Thl和Th2两种不同的亚群，Thl／Th2失衡在自身免疫性甲状腺疾病的发病机制中起重要作用。Graves病可能以Th2型细胞因子介导的体液免疫为主，桥本甲状腺炎可能以Thl型细胞因子介导的细胞免疫为主，而Thl／Th2细胞因子共同参与Graves突眼的形成。     

自身免疫性甲状腺疾病与细胞凋亡

自身免疫性甲状腺疾病细胞凋亡存在异常,桥本甲状腺炎时,甲状腺细胞Fas表达增强,诱导细胞凋亡,造成甲状腺细胞的损伤。Graves病时因Fas表达减弱,bcl-2表达增经而阻止了凋亡生,从而造成甲状腺滤泡上皮细胞增生肥大,一些物质可以上调或者下调甲状腺细胞Fas表达,因此,可能为自身免疫性甲状腺疾病开拓一条新的治疗途径。     

硒治疗自身免疫性甲状腺疾病的荟萃分析

目的 评价元素硒治疗自身免疫性甲状腺疾病(AITD)的有效性和安全性.方法 通过5个数据库(MEDLINE,Cochrane Central Register of Controlled Trials,中国期刊全文数据库,中国生物医学文献数据库和维普数据库)检索所有研究元素硒治疗AITD的随机对照试验(RCT).由两名研究者独立筛选文献、提取数据和进行结果的统计分析.将结果数据形式一致的同类临床试验的结果进行荟萃分析,对不能荟萃分析的数据进行描述性分析.共纳入30项RCT,涉及2 963例AITD患者.结果 (1)与对照组相比,硒治疗组桥本甲状腺炎患者甲状腺过氧化物酶抗体(TPOAb)和甲状腺球蛋白抗体(TgAb)水平明显下降[标准化均数差(SMD)=-1.35,95％ CI:-1.93～-0.67,P ＜0.000 01和SMD=-0.92,95％ CI:-1.53～-0.31,P＜0.01].(2)硒治疗组与对照组相比,Graves病患者促甲状腺激素受体抗体(TRAb)水平降低(均数差=-2.5,95％ CI:-2.99～-2.01,P＜0.000 01).(3)元素硒可以降低Graves病患者血清游离T3(FT3)和游离T4(FT4)水平(均数差=-1.57,95％ CI:-2.56～-0.58,P＜0.001和均数差=-3.74,95％ CI:-5.65～-1.82,P=0.000 01),但对桥本甲状腺炎患者FT3、FT4和促甲状腺激素的作用不明显(P均＞0.05).结论 对AITD患者使用200 μg∥d的元素硒治疗3～12个月,能够有效降低抗甲状腺自身抗体(TPOAb,TgAb和TRAb)的水平,并具有较好的安全性.     

Graves眼病Th1/Th2相关细胞因子群谱的特征

目的　探讨Graves眼病 (Graves’ophthalmopathy ,GO)发生的免疫机制 ,明确GO的Th1/Th2 相关细胞因子群谱的特征。方法　用逆转录聚合酶链反应 (RT PCR)检测IFN γ、TNF α、IL 2、IL 4、IL 6、IL 10等 6种细胞因子的mRNA转录。结果　与正常对照组相比 ,Graves病恶性突眼组与非突眼组细胞因子的基因转录检出率明显增高 (P <0 .0 1) ;Graves病非突眼组Th2 类细胞因子IL 4和IL 6的基因转录检出率明显高于Th1类细胞因子IFN γ ,TNF α和IL 2的基因转录检出率 (P <0 .0 1) ;而恶性突眼组Th1和Th2 之间细胞因子的基因转录检出率差异无显著性 (P >0 .0 5 )。结论　Graves病恶性突眼者细胞因子的基因转录模式呈典型的Th0 ,细胞免疫和体液免疫共同参与了突眼的发生 ,而非突眼者细胞因子表达向Th2 方向漂移 ,以体液免疫应答为主。     

自身免疫性甲状腺疾病中Th1／Th2细胞因子的偏移

细胞因子（cytokine，CK）是由人体免疫细胞产生的一类小分子多肽或蛋白质，它通过和细胞膜表面的特异受体结合而调节细胞的生长、分化、免疫，信息传递及炎症发生、创伤愈合等多种生命过程。根据功能可分为白细胞介素（interleukin，IL）、干扰紊（interferon，IFN）、肿瘤坏死因子（tumor necrosis factor，TNF）、集落刺激因子等不同家族。     

冬虫夏草对慢性阻塞性肺疾病大鼠Th1/Th2类细胞因子平衡的干预作用

迄今为止对慢性阻塞性肺疾病 (ＣＯＰＤ)仍无有效治疗药物供临床使用。我们通过人工培育的冬虫夏草菌粉喂养ＣＯＰＤ大鼠 ,观察组织形态学、动物肺功能 (气道阻力和肺顺应性 )、支气管肺泡灌洗液 (ＢＡＬＦ)中白细胞介素 2 (ＩＬ 2 )、细胞介素ＩＬ 4含量等指标 ,探讨其防治ＣＯＰＤ的作用及机制。材料与方法　雄性ＳＤ大鼠 (清洁级 ) 3 7只 ,体重 (2 0 0±2 0 )ｇ ,随机分为 3组。 (1)模型组 13只 ,在自制吸烟染毒箱内被动吸烟 2 0支 (上海卷烟厂凤凰牌香烟 ,焦油量 17ｍｇ/支 ,烟气烟碱量 1 4ｍｇ/支 ) ,每天 3次 ,每次间隔 3ｈ ,共 60天 …     

Graves病患者甲状腺131I转化率与Th1/Th2细胞因子偏移率的相关性研究

目的探讨Th1/Th2细胞因子偏移对格雷夫斯病（Craves disease,GD）碘转化率之间的相关性。方法选诊断为GD要求¹³¹Ⅰ治疗的60例患者和30例健康对照者,分别测定IL-2代表Th1细胞因子,IL-6代表Th2细胞因子。结果 IL-6在GD组明显高于对照组（P<0.01）;IL-2水平明显低于对照组（P<0.01）。IL-2、IL-6及IL-2/IL-6与甲状腺碘转换率均无明显相关性（P>0.05）。结论 GD患者的Th1/Th2细胞亚群失衡以偏向Th2为主;Th1/Th2细胞的偏移与甲状腺的碘转化率无相关性。     

Th1 and Th2 cytokine profiles in sickle cell disease

We have investigated the levels of Th1 (IL-2 and IFN-gamma) and Th2 (IL-4) cytokines in the plasma and supernatants following peripheral blood mononuclear cell culture and mitogen stimulation in a group of 39 patients with sickle cell disease (SCD) made up of 29 SS, 8 Sbeta-thal and 2 Hb SD in steady state. Five SS patients were studied during 7 episodes of vaso-occlusive crisis. Twenty-four control (3 Hb AS and 21 Hb AA) were also studied; 10 were acutely ill while 14 were healthy at the time of the study. The plasma levels of IL-2 and IFN-gamma were similar in the patients and the controls. However, plasma IL-4 was significantly higher among the steady-state SS patients than in the controls. While there was no significant difference in cytokine levels following mitogen stimulation in the different groups, plasma IL-2 to IL-4 and IFN-gamma to IL-4 ratios were significantly lower among the steady-state SS patients, indicating a possible Th2 bias in our sickle cell patients and suggesting a possible mechanism to explain the predisposition of SCD patients to bacterial infections. However, SS patients with good splenic function showed a relative Th1 bias, which may be an additional explanation for the protection against bacterial infections in such patients.     

Th1/Th2细胞平衡偏移与自身免疫性甲状腺疾病的相关性研究

目的 明确白细胞介素-2(IL-2)、IL-5与自身免疫性甲状腺疾病(AITD)发生的相关性,探讨Th1/Th2细胞平衡在自身免疫性甲状腺疾病发病中的作用.方法 选取2007年8月至2008年5月南昌大学第三附属医院内分泌科45例Graves病(GD)、30例桥本甲状腺炎(HT)患者,同时选取20名健康体检者作为对照组.采用酶联免疫吸附试验法(ELISA)检测患者和对照组血清中Th1型细胞因子IL-2扣Th2型细胞因子IL-5并进行统计学分析.结果 (1)GD患者血清中IL-5明显高于HT组和对照组(P<0.05),而IL-2与对照组相比差异无统计学意义(P>0.05).(2)HT患者血清IL-2明显高于GD组和对照组(P<0.05),而IL-5与对照组相比差异无统计学意义(P>0.05).(3)HT患者Th1型细胞因子IL-2与甲状腺球蛋白抗体(TCAb)和甲状腺微粒体抗体(TMAb)呈显著正相关(r=0.517,P<0.05;r=0.475,P<0.01).结论 Th1/Th2细胞免疫平衡在HT患者中以Th1细胞免疫占优势为主,在GD患者中以Th2细胞免疫占优势为主.     

A cyclooxygenase-2 inhibitor alters Th1/Th2 cytokine balance and suppresses autoimmune myocarditis in rats

Acute myocarditis is a clinically serious disease; however, no effective treatment has been elucidated. Cyclooxygenase (COX)-2 is a key factor for progression of inflammation. Although inflammation is an essential pathological feature of acute myocarditis, the role of COX-2 in this process remains unclear. Thus, the purpose of this study was to clarify the role of COX-2 in acute myocarditis. We used a rat experimental autoimmune myocarditis (EAM) model and a specific COX-2 inhibitor in this study. Lewis rats were immunized on day 0 with porcine cardiac myosin to establish EAM. We administered the COX-2 inhibitor (meloxicam, 0.1 mg/kg per day) daily; the rats were killed on day 21. Echocardiograms, body and heart weight, heart rate, blood pressure, and histological and molecular examinations were performed. Cytokine expression in the hearts and cell proliferation against cardiac myosin were also analyzed. The COX-2 inhibition during the immune response (late) phase attenuated EAM development; however, the inhibition during the antigen priming (early) phase did not attenuate EAM. The COX-2 inhibitor altered Th1/Th2 cytokine balance and inhibited cell proliferation in vitro. The COX-2 inhibitor suppresses the development of EAM. COX-2 regulation is promising for treating acute myocarditis.     

Th1 and th2 cytokine profiles in malignant pleural effusion

Background: The alteration of Th1 and Th2 cytokine levels is the subject of controversy in pleural effusions caused by malignancy, a situation that favors a Th2 immune response. Objective: To examine the different levels of IL-4 and IL-10 (Th2 cytokines), and IL-2 and interferon-γ (IFN-γ) (Th1 cytokines) in malignant and non-malignant pleural effusions. Method: The cytokine levels in pleural fluid of 62 patients with malignant pleural effusion (44 with lung cancer and 18 with extrathoracic tumors), 8 with tuberculous and 8 with congestive heart failure pleural effusion were analyzed using enzyme-linked immunosorbent assays. Results: IL-2 was below the detectable concentration of the assay. A significant decrease in IFN-γ level was observed in malignant but not in congestive heart failure cases compared to tuberculous cases. IL-10 levels were higher in malignant and tuberculous pleural effusions than in congestive heart failure pleural effusions, however, this difference did not reach the significant level. IL-4 levels were also increased non-significantly in lung cancer pleural effusions compared to the other groups. Conclusion: Our results show a wide variation in IL-4, IL-10, and IFN-γ levels in malignant pleural effusions, a pattern which was not convincing enough to differentiate the cause of effusion.     

Evaluation of intravenous immunoglobulin resistance and coronary artery lesions in relation to Th1/Th2 cytokine profiles in patients with Kawasaki disease

Objective

To investigate the roles of serum Th1 and Th2 cytokines in Kawasaki disease (KD) and determine whether the Th1/Th2 cytokine profiles in children with KD may be involved in intravenous immunoglobulin (IVIG) resistance and development of coronary artery lesions (CALs).

Methods

Serum Th1 and Th2 cytokines, including interferon‐γ (IFNγ), tumor necrosis factor α (TNFα), interleukin‐10 (IL‐10), IL‐6, IL‐4, and IL‐2, were measured using a cytometric bead array in the serum of 143 patients with KD before and after treatment with IVIG (pre‐IVIG, at 3 days after temperature normalization following IVIG treatment [post‐IVIG], and 1 month posttreatment).

Results

Levels of IL‐6, IL‐10, TNFα, and IFNγ were significantly increased in KD patients pre‐IVIG. Post‐IVIG, the levels of IL‐6, IL‐10, and IFNγ quickly decreased. The levels of TNFα decreased significantly after IVIG treatment in KD patients without CALs post‐IVIG and in KD patients who were IVIG responders, but increased slightly in KD patients with CALs post‐IVIG and in KD patients who were IVIG nonresponders. Before IVIG treatment, the levels of IL‐4, IL‐6, IL‐10, and IFNγ were significantly higher in KD patients with CALs than in those without CALs. The post‐IVIG levels of IL‐6 and IL‐10 were significantly higher in IVIG nonresponders than in IVIG responders. Pre‐IVIG, an IL‐10 level >8 pg/ml had a sensitivity of 75.0% and a specificity of 64.4% for predicting CALs, while a TNFα level <2 pg/ml had a sensitivity of 66.7% and a specificity of 74.2% for predicting IVIG resistance. Post‐IVIG, an IL‐6 level >10 pg/ml had a sensitivity of 67.9% and a specificity of 81.7% for predicting CALs, while an IL‐10 level >6 pg/ml had a sensitivity of 53.6% and a specificity of 86% for predicting CALs.

Conclusion

Determination of the serum Th1/Th2 cytokine profile may be helpful for predicting the disease prognosis and targeting treatment strategies in patients with KD.

     

狼疮肾炎患者Th1/Th2细胞因子失平衡状况的研究

目的探讨不同病理类型、不同病程狼疮肾炎(LN)患者的Th1和Th2失衡情况。方法采用酶联免疫吸附试验(ELISA)法测定16名正常人及18例LN患者外周血浆白细胞介素(IL)-18及IL-13水平,同时应用免疫组织化学检测6名正常人肾组织和18例LN患者肾组织IL-18及IL-13的表达量。结果无论在肾组织或外周血,LN患者IL-18水平及IL-13水平均较正常对照组显著上升(P均<0.001),Ⅳ型LN患者血浆IL-18/IL-13较正常对照组显著增高(P<0.05),V型LN患者较正常对照组有降低趋势,但未达统计学意义(P>0.05),而Ⅱ型LN患者其比率数值与正常对照组极其接近;在肾组织局部,不同病理类型LN患者之间IL-18/IL-13比率差异无显著性(P>0.05);血浆IL-18/IL-13比率与肾组织狼疮活动指数(AI)呈正相关(P<0.05),肾组织IL-18/IL-13比率与AI无相关关系(P>0.05)。结论LN患者免疫紊乱状态似乎不能简单的按Th1优势/Th2优势进行二分法分类,其免疫紊乱状态远较此复杂,不同活动状态,不同部位及不同病理类型的狼疮的免疫紊乱状态是不同的。