Therapeutic effect of mesenchymal stem cell on Hashimoto’s thyroiditis in a rat model by modulating Th17/Treg cell balance

Abstract

The autoimmune condition Hashimoto’s thyroiditis (HT) is a disease wherein lymphocytes mediate the autoimmune damage and destruction of the thyroid gland. There are currently no effective means of treating HT, with the primary strategies of thyroid hormone therapy, surgery, or immunomodulatory therapy being associated with serious risks and side effects. There is thus a clear and urgent need to identify novel treatments for HT. In this study, we utilize female SD rats induced HT to evaluated the ability of transplanted MSCs to regulate Th17/Treg interactions in a rat Hashimoto’s thyroiditis (HT) model system. The results showed that Rats in the HT model group exhibited increased thyroid autoantibody levels consistent with successful model development, whereas these levels were lower in rats treated with MSCs. There were also fewer thyroid lesions and less lymphoid infiltration of the thyroid in MSC-treated rats relative to HT model rats, as well as fewer Th17 cells and more Treg cells – an observation consistent with the cytokine analyses. All of these showed that MSCs can regulate Th17/Treg interactions in a rat Hashimoto’s thyroiditis (HT) model system. It suggested that transplanted MSCs could be a potential immunotherapy strategy for the treatment of Hashimoto’s thyroiditis.     

体外培养骨髓单个核细胞分泌促血管生长因子的实验研究

目的分析体外培养的骨髓单个核细胞持续分泌促血管生长因子的能力。方法从大鼠胫骨及股骨采集骨髓,密度梯度离心法分离出骨髓单个核细胞进行体外培养,并连续收集4周培养上清液。酶联免疫吸附实验(ELISA)法测定培养上清液中碱性成纤维细胞生长因子(bFGF)、血管内皮细胞生长因子(VEGF)和白介素-1β(IL-1β)等因子水平。结果第1、2、3、4周骨髓单个核细胞体外培养上清液中VEGF分别为(24.40±7.99)pg/m、l(89.28±5.13)pg/m、l(115.24±10.08)pg/m、l(157.00±15.64)pg/m l;bFGF含量分别为(52.72±2.13)pg/m、l(48.10±6.41)pg/m、l(44.71±3.21)pg/m、l(25.61±2.42)pg/m l;IL-1β含量分别为:(31.28±5.44)pg/m、l(71.87±3.01)pg/m、l(55.77±11.94)pg/m、l(41.75±9.14)pg/m。l结论体外培养骨髓单个核细胞可持续分泌VEGF、bFGF、IL-1β等多种促血管生长因子。     

白细胞介素-8在哺乳动物生殖过程中的作用

白细胞介素-8(IL-8)作为中性粒细胞趋化因子和促血管生成因子,受到人们的重视。研究表明,IL-8促进卵细胞的发育、成熟,诱发排卵;在输卵管和子宫内膜的表达随月经周期而变化;参与胚泡着床和胚胎发育。本文综述IL-8在哺乳动物生殖过程中的重要作用。     

IL-10在过敏性紫癜血管内皮损伤中的作用机制研究

目的　探讨白细胞介素 10 (IL 10 )在过敏性紫癜血管内皮损伤中的作用及机制。方法　建立人脐静脉内皮细胞 (HUVEC)培养模型 ,ELISA法检测过敏性紫癜患儿外周血单个核细胞 (PB MC)活化后培养上清IL 6、IL 1β、TNF α、IL 10等细胞因子的含量 ;AnnexinV/PI双染色法 ,流式细胞仪检测过敏性紫癜患儿PBMC培养上清所诱导的内皮细胞凋亡率。结果　①过敏性紫癜组PBMC体外刺激活化后IL 6、IL 1β、TNF α、IL 10等细胞因子的分泌量均明显高于对照组 (P <0 0 1) ,其培养上清诱导的内皮细胞凋亡率 (34 7± 10 3) %明显高于对照组 (3 6± 0 9) %。②抗IL 6、IL 1β、TNF α单克隆抗体联合阻断可明显降低过敏性紫癜患儿PBMC培养上清诱导的内皮细胞凋亡率 (2 2 6±5 9) % ,而抗IL 10单克隆抗体阻断则明显增加过敏性紫癜患儿PBMC培养上清诱导的内皮细胞凋亡率 (5 6 9± 16 5 ) %。③于过敏性紫癜患儿PBMC培养上清加入外源性IL 10 ,可明显降低IL 6、IL 1β、INF α等炎性细胞因子的表达 ,并明显降低内皮细胞凋亡率 (11 8± 3 1) %。结论　IL 10作为机体炎症反应负反馈调节过程中的一个重要枢纽 ,在过敏性紫癜炎症因子所介导的血管内皮损伤中起重要的保护作用。     

新化合物 A-失碳-17β-羟基-17α-乙炔基-Δ3(5),9(10)-雌甾二烯-2-酮的合成

报道新化合物A-失碳-17β-羟基-17α-乙炔基-Δ^3(5),9(10)-雌甾二烯-2-酮2的合成。文中探讨了用炔钾粗品对A-失碳-Δ^3(5),9(10)-雌甾二烯-2，17-二酮１和Ａ-失碳-６β，１９-环氧-Δ³-雄甾-2，17-二酮3的选择性炔化，分别得标题化合物2（44%）及Ａ-失碳-17β-羟基-17α-乙炔基-６β，１９-环氧-Δ³雄甾-2-酮４（６５％），４经还原性破开环氧、去羟甲基和去醋酰氧基合成了标题化合物２。四步总收率为３４％。     

Catabolic effects and the influence on hormonal variables under treatment with gynodian-depot® or dehydroepiandrosterone (DHEA) oenanthate

53 patients from a mainly climacteric population were treated monthly with 200 mg dehydro-epiandrosterone (DHEA) oenanthate or with 1 ampoule Gynodian-Depot®. Pronounced adiposity was present in 15 of these cases. Hormonal variables were determined before the treatment and during the depot effect of the preparations in order to study the principle which supports the oestrogenic influence and any weight-reducing influence under administration of DHEA. The elimination of lowpolar oestrogens increased considerably in 4 out of 13 post-menopausal cases treated with DHEA. This effect is probably indirect and presupposes intact ovaries. The incorporation of exogenous DHEA into the excretion of 17-ketosteroids and of 17-ketogenic steroids, such as those of androsterone + aethiocholanolone, depends on the size of the initial pool inasmuch as it is higher in small initial pools than in saturated pools - the size of the pool being age-dependent.

An average weight loss of >1 kg/mth was observed under DHEA treatment in 7 out 15 adipose cases. In comparison to the other 8 adipose cases, these 7 were younger and therefore also displayed higher values for 17-ketosteroids and their individual fractions. These circumstances appeared to explain why the administration of DHEA resulted in higher levels of free plasma DHEA which, in contrast to the cases without loss of weight, also resulted in an increase of renal DHEA-sulphate clearance. It was concluded from the findings that this is the explanation for the catabolic effect of exogenous DHEA.

Post-menopausally increased FSH and LH fractions were markedly suppressed in about half of the determinations after Gynodian-Depot administration, the findings indicating that DHEA is probably involved in suppression of the LH fraction.     

Antibodies to interleukin-1 inhibit cytokine-induced proliferation of neonatal rat Schwann cells in vitro

Unfractionated cytokines have been shown to induce in vitro proliferation of neonatal rat Schwann cells but the nature of the mitogen(s) is not known. A mixture of rabbit antibodies specific for recombinant interleukin-1α (IL-1α) and interleukin-1β (IL-1β) inhibited Schwann cell proliferation induced by unfractionated human cytokines whereas antibodies to interleukin-2 (IL-2) and control IgG did not. However, purified human IL-1 and recombinant human IL-1α or β did not induce Schwann cell proliferation on their own.     

Effects of antimicrobial agents on spontaneous and endotoxin-induced cytokine release of human peripheral blood mononuclear cells

 Because the immunomodulatory effects of antibiotics could possibly influence the degree of the systemic and local response to infection, knowledge of their intrinsic influence on the host's inflammatory response appears to be essential. Therefore, this study investigated the effects of frequently used antimicrobial agents (β-lactams, quinolones gentamicin, vancomycin and metronidazole) on the in-vitro tumor necrosis factor (TNF)-α and interleukin (IL)-6 production of isolated human peripheral blood mononuclear cells (PBMNC), cultured with or without endotoxin, in comparison with those effects obtained in a whole-blood assay system. In the presence of ciprofloxacin, ofloxacin, gentamicin, vancomycin, and metronidazole, a significant inhibition of the endotoxin-stimulated TNF-α production of human peripheral blood mononuclear cells (PBMNC) was found at therapeutic levels. Only ofloxacin showed a significant inhibitory influence on the endotoxin-induced IL-6 production of PBMNC. In the whole-blood assay, significant effects were not detectable. None of the antibiotics showed cytotoxicity. It is concluded that, at present, the direct immunological effects of antibiotics should be interpreted carefully with regard to the experimental conditions, and regardless of the therapeutic implications. To assess the potential direct immunomodulatory effect of antimicrobial agents, different cell culture procedures should be used. Received: October 19, 2001 / Accepted: February 15, 2002     

Open, Double-Blind and Long-Term Study of Vigabatrin in Chronic Epilepsy

We performed an open, double-blind, and long-term study of vigabatrin (gamma-vinyl-GABA, GVG) in patients with treatment-resistant epilepsy who were receiving only one or at most two standard antiepileptic drugs (AEDs). The novel design included a parallel, double-blind, placebo-controlled phase that minimized the number of patients receiving placebo and allowed determination of the optimum dose of GVG for each patient before initiation of the double-blind phase. The study was divided into four phases. The first phase was a 6-week period of baseline observation. In the second phase, GVG was added openly to previous AEDs for 8 weeks. During the first 2 weeks of this phase, the dose of GVG was increased weekly and then, in the absence of adverse effects, was held constant for the next 6 weeks. At the end of this open phase, seizure frequency during the 6 weeks of constant treatment was compared with the baseline seizure frequency for each patient. Patients who experienced reduction greater than 50% in the frequency of any seizure type during the open phase were defined as responders. These responders were then entered into the third and double-blind phase, in which they were randomly allocated wither to continue active GVG treatment or placebo for 8 weeks. Thirty-three patients entered the study; 31 of 33 patients completed the initial open phase. Twenty patients achieved a reduction greater than or equal to 50% in the frequency of one or more seizure types and were eligible for the double-blind phase; 10 were randomized to continue GVG and 10 were randomized to placebo.(ABSTRACT TRUNCATED AT 250 WORDS)