调节性及辅助性T细胞在人类IgA肾病中的表达及意义

目的 探讨CD4+CD25high调节性T细胞（Treg）及辅助性T细胞亚群（Th1、Th2）比例失衡在IgA肾病（IgAN）免疫发病机制中的作用。 方法 用流式细胞仪检测IgAN患者外周血Treg及Th1、Th2的比例。以胞内染色技术检测叉头框蛋白3（FOXP3）的表达。Treg及Th1、Th2的比例与IgAN各项临床病理指标的相关性分析采用Spearman或Pearson相关分析法。 结果 IgAN患者外周血中Treg比例明显高于健康人[（2.14±0.82）％比（1.59±0.53）％，P ＜ 0.05]，与血IgA水平呈正相关（r = 0.397，P ＜ 0.05），与eGFR呈负相关（r = -0.376，P ＜ 0.05）。IgAN患者外周血中Th2细胞比例显著高于健康对照组[（2.57±0.72）％比（1.81±1.10）％，P ＜ 0.05]，与血IgA水平呈正相关（r = 0.468，P ＜ 0.05）。IgAN患者Th1/Th2比值显著低于健康对照组（5.75±1.89比12.73±9.79，P ＜ 0.05），但与临床各指标间没有相关性。 结论 IgAN患者体内存在T细胞亚群表达紊乱。Treg在外周血中的增多以及以Th2为优势的Th1/Th2失衡可能在IgAN的发病中起重要作用。     

雷公藤多苷对IgA肾病CD4＋CD25high调节性T细胞及Th1、Th2影响

目的：探讨CD4＋CD25high调节性T细胞（Treg）及辅助性T细胞亚群（Th1、Th2）比例失衡在IgA肾病（IgAN）免疫发病机制中的作用,以及使用雷公藤多苷（tripterygium wilfordii glycoside,TW）治疗后对IgAN 的 Treg、Th1、Th2及Th1/Th2的比例影响.方法：用流式细胞分析仪检测30例IgAN患者,使用雷公藤多苷治疗前后的外周血Treg、Th1、Th2及Th1/Th2的比例.并与健康对照组进行比较,两组间比较采用t检验.结果：IgA N患者外周血Treg的比例明显高于健康人（P＜0.01）;IgAN患者外周血中,Th2细胞比例显著高于健康对照组（P＜0.01）;IgAN患者Th1/Th2比值显著低于健康对照组（P＜0.01）.使用TW （1 mg·kg-1·d-1）治疗 IgAN 3个月后,可显著降低IgAN患者外周血Treg（P＜0.01）,但治疗后Treg仍高于健康对照组（P＜0.05）;显著降低Th2细胞比例（P＜0.05）,显著升高Th1/Th2比值（P＜0.01）;且治疗后IgAN的尿蛋白明显降低（P＜0.01）,血清白蛋白升高（P＜0.05）.结论：TW可改善IgAN患者体内存在T细胞亚群表达紊乱,对IgAN治疗具有一定作用.     

The imbalance between regulatory and IL-17-secreting CD4T cells in multiple-trauma rat

Background

It has been well recognised that a deficit of numbers and function of CD4⁺CD25⁺Foxp3⁺cells (Treg) is attributed to the development of auto-immune diseases, inflammatory diseases, tumour and rejection of transplanted tissue; however, there are controversial data regarding the suppressive effect of Treg cells on the T-cell response in auto-immune diseases. Additionally, interleukin-17 (IL-17)-producing cells (Th17) have a pro-inflammatory role. The balance between Th17 and Treg may be essential for maintaining immune homeostasis and has long been thought as one of the important factors in the development/prevention of auto-immune diseases, inflammatory diseases, tumour and rejection of transplanted tissue, but their role in multiple trauma remains unclear.

Objective

This study aims to investigate whether an imbalance of Treg and Th17 effector cells is characteristic of rats suffering from multiple trauma.

Methods and subjective

Sixty Sprague-Dawley (SD) rats were randomly divided into three groups. The control group (n = 20, group I) no received procedures (normal). The sham group (n = 20, group II) only received anaesthesia, cannulation and observation. The bilateral femoral shaft fractures with haemorrhagic shock groups (n = 20, group III). Rats in groups II and III were killed at the end of 4 h after models were established. Peripheral blood samples were collected for assessment of Treg cells, Th17 cells and cytokines (IL-17, IL-6, IL-2, transforming growth factor beta (TGF-β)) and intestine tissue was collected for intestine histological analysis.

Results

We observed decreased Treg/Th17 ratios in CD4⁺T cells in rats with multiple trauma and a strong inverse correlation with disease activity (intestinal histological scores).

Conclusion

We suggest a role for immune imbalance in the pathogenesis and development of multiple trauma. The alteration of the index of Treg/Th17 cells likely indicates the therapeutic response and progress in the clinic.     

原发性肝癌患者外周血Th17与CD4^＋CD25^＋调节性T细胞表达的相关性研究

目的探讨原发性肝癌患者外周血Th17和CD4^＋CD25^＋调节性T细胞的表达水平及其相关性。方法选取2008年6月—2009年5月浙江大学医学院附属第一医院30例原发性肝癌患者和25名健康人群,采血并分离其外周血单个核细胞。利用流式细胞仪分别测定Th17和CD4^＋CD25^＋Foxp3^＋调节性T细胞的表达,采用t检验分析两组的表达差异。同时,采用Spearman检验对原发性肝癌患者外周血中Th17和CD4^＋CD25^＋调节性T细胞的表达进行相关性分析。结果健康对照组外周血中Th17细胞为（2．10±0．87）％,CD4^＋CD25^＋调节性T细胞为（7．10±2．32）％,原发性肝癌组外周血中Th17细胞为（3．38±1．68）％,CD4^＋CD25^＋调节性T细胞为（11．78±5．62）％,两组差异具有统计学意义（t=3．640和4．162,P值均〈0．01）。原发性肝癌患者组外周血Th17细胞与CD4^＋CD25^＋Fosp3^＋调节性T细胞表达呈正相关（r=0．821,P〈0．01）。结论原发性肝癌患者外周血Th17和CD4^＋CD25^＋Fosp3^＋调节性T细胞表达水平较高,二者呈正相关。CD4^＋CD25^＋Fosp3^＋调节性T细胞可能通过促进Th17细胞分化导致肿瘤的发生与发展。     

干预协同刺激信号诱导不明原因早期复发性流产患者外周血Th1/Th2转换的体外研究

目的观察体外干预细胞毒性T细胞相关抗原4(CTLA-4)对不明原因早期复发性流产(URSA)患者外周血辅助性T细胞(Th)1/Th2转换的影响。方法用人绒毛膜癌细胞株JEG-3制备的滋养细胞抗原刺激30例URSA患者外周血单核细胞,分为实验组A:加重组蛋白CTLA-4Ig(10和1 mg/L)组,实验组B:加CTLA-4抗体(10和1 mg/L)组;对照组:加IgG(10和1 mg/L)组。采用酶联免疫吸附试验(ELISIA)测上清液中白细胞介素(IL)-2、干扰素γ(IFN-γ)和IL-4水平。结果与相应浓度的对照组相比,CTLA-4Ig组IL-4水平显著升高(P<0.05),IL-2显著降低(P<0.05),IFN-γ两组间无显著性差异(P>0.05);而CTLA-4抗体组IL-4水平均显著低于对照组(P<0.01),而IFN-γ、IL-2水平均明显高于对照组(P<0.05)。CTLA-4Ig 10 mg/L组与CTLA-4Ig 1mg/L组比较,IL-4显著升高(P<0.05),IL-2显著降低(P<0.05),IFN-γ两组间无显著性差异(P>0.05)。与同浓度的对照组及CTLA-4抗体1 mg/L组相比,CTLA-4抗体10 mg/L组IL-4较低,而IFN-γ和IL-2稍高,但两组间亦无显著性差异(P>0.05)。结论CTLA-4Ig使URSA患者Th1/Th2型细胞因子向Th2型细胞因子偏移,有利于URSA的治疗;而CTLA-4抗体可以上调Th1型细胞因子,下调Th2型细胞因子,不利于妊娠。     

Imiquimod regulating Th1 and Th2 cell‐related chemokines to inhibit scar hyperplasia

Immunological factors play important roles in the occurrence of hypertrophic scars. Imiquimod can be used as an immunosuppressive agent to regulate the function of T‐helper (Th) cell subsets Th1 and Th2. In this article, we explored the impact of imiquimod on scar hyperplasia through Th cells. A rabbit ear hypertrophic scar model was built. Four round wounds were cut in each rabbit's ears ventrally with a diameter of 1 cm and bilateral symmetry. All the right ear wounds were treated with 5% imiquimod cream. The blank control group contained all the left ear wounds, which were treated with Vaseline ointment at the same time. Haematoxylin and eosin and Masson staining showed that imiquimod collagen deposition was significantly reduced compared with the control group, scar index (SEI) showed that the proliferative degree reached its peak on the 28th day after operation in blank group, and the degree of hyperplasia was significantly higher than that of the imiquimod group (P < .05). Real‐time Polymerase chain reaction results showed that the imiquimod induced the expression of Th2 cell‐related chemokines CCL2, CCL3, CCL5, CCL7, and CCL13 at each time point, which were significantly lower than that of the blank control group, and the expressions of Th1 cell‐associated chemokines CXCL10 and CXCL12 at each time point was significantly higher than the blank control group (P < .05). Imiquimod can be used to regulate the expression of Th1 and Th2 cell‐associated chemokines to control scar hyperplasia.     

Non‐Classical Pathways of Cell‐Mediated Allograft Rejection: New Challenges for Tolerance Induction?

Allograft rejection results from separate pathways primarily controlled by CD4+ T cells. Refinement of transplantation models together with investigations on rejection occurring despite co-stimulation blockade revealed unexpected pathways involving CD8+ T cells, NK cells and Th2 cytokines. In this minireview, we discuss these non-classical pathways of allograft rejection and their relevance for the induction of tolerance in the clinics.     

尿胞外体1型辅助性T细胞/2型辅助性T细胞失衡与2型糖尿病肾病的相关性

目的 探讨2型糖尿病（DM）患者尿胞外体1型辅助性T细胞/2型辅助性T细胞（Th1/Th2）的变化与2型糖尿病肾病（DN）发生发展的相关性。 方法 选取120例2型糖尿病患者及健康对照组30例为对象,根据尿白蛋白肌酐比（UACR）,2型糖尿病患者分为糖尿病非肾病组（DM,40例,UACR<30 mg/gCr）、微量白蛋白尿组（DN1,50例,UACR≥30~300 mg/gCr）和临床白蛋白尿组（DN2,30例,UACR＞300 mg/gCr）。用特异性单克隆抗体提纯尿胞外体。用酶联免疫吸附法（ELISA）检测尿胞外体干扰素γ（IFN-γ）和白细胞介素4（IL-4）水平。用多元逐步回归方法分析尿胞外体IFN-γ/IL-4比值与糖化血红蛋白（HbA1c）、胆固醇（CH）、UACR、血肌酐（Scr）、尿素氮（BUN）相关性。 结果 DM、DN1、DN2组胞外体Th1/Th2水平显著高于健康对照组（0.8089±0.2458、0.8993±0.3515、0.8571±0.2470比 0.6198±0.1769,均P < 0.01）。DN1组胞外体Th1/Th2显著高于DM组（P < 0.01）。尿胞外体IFN-γ/IL-4与UACR（r = 0.213,P = 0.015）、BUN（r=0.292,P = 0.001）呈正相关。逐步多元回归分析显示, BUN是尿胞外体IFN-γ/IL-4的独立影响因素（β = 0.246,P = 0.006）。 结论 尿胞外体Th1/Th2漂移与2型糖尿病肾病密切相关,可能在糖尿病早期肾病发病过程中起重要的作用。     

Rat Renal Interstitial Fibroblasts Affect the Th1/Th2 Profile In Vitro

Background: T helper 1 (Th1)/T helper 2 (Th2) profile is pivotal in the development of fibrosis. Renal interstitial fibroblasts, which play a central role in the development of renal interstitial fibrosis, have an intimate relation with lymphocytes. However, there is little knowledge of the effect of fibroblasts on the profile of CD4 T-lymphocyte subsets. Methods: After coculture with rat renal interstitial fibroblasts, the proportions of Th1 and Th2 cells in CD4 T lymphocytes and the apoptosis rates of the two subsets were detected by flow cytometry. Galectin-9 expression in rat renal interstitial fibroblasts was detected by immunofluorescence, Western blotting, and enzyme-linked immunosorbent assay. Results: After 48 h of coculture, rat renal interstitial fibroblasts increased the proportion of Th2 cells, lowering the ratio of Th1/Th2. Meanwhile, interferon-gamma production in Th1 cells was inhibited and interleukin-4 production in Th2 was promoted. After coculture with activated rat renal interstitial fibroblasts for 24 h, apoptosis of Th1 was more highly promoted than that of Th2 cells. In addition, rat renal interstitial fibroblasts induced stronger Th2 cell differentiation than that of Th1 cells in vitro. Rat renal interstitial fibroblasts expressed but did not secrete galectin-9 (an apoptosis-inducing factor for Th1 cells) in vitro and the expression level decreased when cocultured with CD4 T lymphocytes. Conclusions: Rat renal interstitial fibroblasts shift the Th1/Th2 profile in vitro, and this may be another pathway by which renal interstitial fibroblasts promote fibrosis.     

槐杞黄干预小鼠IgA肾病模型的疗效观察以及机制探讨

目的：探讨槐耳菌质、枸杞子和黄精组方（简称槐杞黄）对免疫性肾病的疗效及其机制。方法：雌性BABL/c小鼠随机分为3组,即正常对照组、IgA肾病模型组、槐杞黄治疗组,每组10只。IgA肾病组和槐杞黄治疗组用牛血清白蛋白酸化水灌胃、牛血清白蛋白以及葡萄球菌肠毒素尾静脉注射免疫建立IgA肾病模型,正常对照组以酸化水灌胃,磷酸盐缓冲溶液尾静脉注射作为对照。槐杞黄治疗组于免疫8周后按4g/kg体重给予槐杞黄浸膏干预,正常对照组、IgA肾病模型组以等量的生理盐水作为对照。观察3组小鼠血清白蛋白、尿素、肌酐24h尿蛋白变化以及肾脏病理改变。12周后处死小鼠,无菌分离脾淋巴细胞,并将各组细胞悬液接种于24孔板中置于37℃、50ml/LCO2条件下孵育51h。用ELISA方法检测各组培养细胞上清中细胞因子IL-2、IL-4、INF-γ的水平,比较各组小鼠INF-γ/IL-4的比值。留取血清,用ELISA方法定量检测血清总IgA的浓度,比较各组动物血清IgA水平。结果：1）第八周和第十二周模型组24h尿蛋白均较对照组明显增加（P〈0.05）,治疗前（8周）槐杞黄治疗组和模型组24h尿蛋白差异无统计学意义（P〉0.05）,治疗4周后,槐杞黄治疗组24h尿蛋白较模型组明显降低（P〈0.05）;2）实验结束时模型组血清白蛋白较对照组明显下降（P〈0.05）,槐杞黄治疗组血清白蛋白较模型组明显升高（P〈0.05）;尿素氮、肌酐含量三组之间差异无统计学意义;3）病理检查显示对照组无明显异常,模型组出现较显著的肾小球系膜细胞增生和系膜基质增多,毛细血管袢受压,开放欠佳,且免疫荧光显示肾小球系膜区和毛细血管壁有较强的颗粒状或者团块状IgA沉积;槐杞黄治疗组肾小球系膜细胞增生和系膜基质增多情况和IgA沉积程度较模型组明显减轻,毛细血管袢开放良好;4）模型组IL-2、INF-γ的分泌较对照组下降（P〈0.01）、IL-4分泌较对照组升高（P〈0.01）;槐杞黄治疗后的IL-2、INF-γ的分泌较模型组升高（P〈0.01）,IL-4分泌较模型组下降;5）模型组INF-γ/IL-4的比值较对照组下降（P〈0.05）,槐杞黄治疗组INF-γ/IL-4的比值较模型组升高（P〈0.01）,血清总IgA的浓度模型组较对照组升高（P〈0.01）,槐杞黄治疗组较模型组降低（P〈0.05）。结论：槐杞黄治疗可以显著减少小鼠IgA肾病尿蛋白,减轻肾小球系膜增生。其机制可能与其上调IL-2、INF-γ表达以及下调IL-4表达,纠正Thl/Th2失衡的作用密切相关。     

Th17/Treg细胞失衡参与类风湿关节炎发病机制的研究进展

类风湿关节炎（rheumatoid arthritis,RA）是一种以滑膜炎和血管炎为特征的自身免疫性疾病,T淋巴细胞浸润是其发病的关键,Th17和Treg细胞具有同源性,皆由初始CD4+ T细胞分化而来。其中Th17 细胞促进炎症反应,而Treg细胞抑制炎症反应,维持自身免疫耐受。RA的发生与免功能疫紊乱、免疫细胞过渡活化以及免疫细胞亚群比例失衡密切相关。Th17/Treg失衡存在整个RA疾病过程中,最终导致滑膜炎症、关节破坏、骨侵蚀等,加重RA病程的发展。调节Th17/Treg之间的平衡是治疗RA的一个靶点。笔者将对Th17/Treg失衡在RA发生发展中的调节作用进行综述。     

High Pre-Transplant Soluble CD30 Levels are Predictive of the Grade of Rejection

In renal transplantation, serum soluble CD30 (sCD30) levels in graft recipients are associated with increased rejection and graft loss. We investigated whether pre-transplant sCD30 concentrations are predictive of the grade of rejection. Pre-transplant sera of 51 patients with tubulointerstitial rejection (TIR), 16 patients with vascular rejection (VR) and an age-matched control group of 41 patients with no rejection (NR) were analyzed for sCD30. The transplant biopsies were immunostained for C4d. The median sCD30 level was significantly elevated in the group with VR (248 Units (U)/mL, range: 92-802) when compared with TIR (103 U/mL, range: 36-309, p<0.001) and NR (179 U/mL, range: 70-343, p<0.03). Moreover, patients with TIR had significantly lower sCD30 levels compared to NR. Based on C4d staining, a TH2 driven process, the median sCD30 levels were significantly raised in C4d+ patients compared with C4d- group (177 U/mL vs. 120 U/mL, p<0.05). sCD30 levels measured at time of transplantation correlate with the grade of rejection. High pre-transplant levels are associated with antibody-mediated rejection which carries a poorer prognosis. sCD30 could be another tool to assess immunological risk prior to transplantation and enable a patient centered approach to immunosuppression.     

慢性非细菌性前列腺炎辅助性T细胞亚群分化及其对炎症的影响

目的：了解慢性非细菌性前列腺炎（CP）前列腺液（EPS）中Th类细胞亚群分化及其和局部炎症的关系。方法：对47例CP患者（CP组）,根据炎症程度分成Ⅰ组（轻度炎症）26例和Ⅱ组（重度炎症）21例;另以16例健康者为对照组。采用双抗体夹心酶联免疫法法检测各组EPS中Th1类细胞因子（IFN-γ）、Th2类细胞因子（IL-4）水平,以及Th1／Th2比值（IFN-γ／IL-4）。结果：与对照组比较,CP组IFN-γ、IFN-γ／IL-4明显升高（P〈0．05）,IL-4水平无明显变化;其中,Ⅰ组IL-4水平无明显变化,而Ⅱ组IL-4水平显著性下调（P〈0．05）;Ⅱ组和Ⅰ组IFN-γ水平均明显上调（P〈0．05）,但此两组间水平无显著性差别;Ⅱ组IFN-γ／IL-4明显高于Ⅰ组（P〈0．05）。结论：CP患者Th1细胞分化占优势,以细胞免疫反应为主;Th1的极化可能是导致前列腺局部炎症发展原因之一。     

Retinoic acid attenuates acute heart rejection by increasing regulatory T cell and repressing differentiation of Th17 cell in the presence of TGF‐β

Retinoic acid (RA), in a transforming growth factor beta (TGF‐β)‐dependent manner, promotes differentiation of regulatory T cells (Tregs) but inhibits the differentiation of Th17 cells in vitro from naive CD4⁺T cells. In addition, transfer of induced Tregs (iTregs) reduces rejection. We therefore examined whether RA could attenuate acute cardiac transplant rejection in vivo in a mouse model by regulating the reciprocal differentiation of Tregs and Th17 cells. The iTregs and naive T cells were respectively transferred into congenic mice. Two weeks later, the percentages of transferred cells and Forkhead box P3 (FoxP3)+ Tregs were measured in spleen. Mice with cardiac transplants were treated with TGF‐β alone, RA alone, both or none. The percentage of Tregs or Th17 cells in CD4⁺T cells, the level of FoxP3 protein or serous interleukin (IL)‐17A, or suppressive function of Tregs from recipient mice were assessed. The percentage of Th17 cells and level of serum IL‐17A both increased significantly during acute rejection. RA favored differentiation to Tregs over Th17 cells. Unlike naive T cells, only a few transferred iTregs remained after transfer. Treatment with RA plus TGF‐β prolonged graft survival, increased the percentage of Tregs, and decreased the percentage of Th17 cells in peripheral T cells. Tregs from all recipients had normal suppressive function. In conclusion, treatment with RA plus TGF‐β attenuates acute rejection by promoting the differentiation of Tregs and inhibiting the differentiation of Th17 cells.     

瘢痕患者免疫功能状态研究

目的：通过比较不同程度瘢痕患者和健康对照组的细胞免疫和体液免疫的差异,分析瘢痕患者免疫功能状态,探讨瘢痕可能的免疫学发生机制。方法：101例瘢痕患者分为三组：轻度瘢痕组、中度瘢痕组和重度瘢痕组。选择健康体检者50例做为正常对照组。测定T细胞亚群比例和CD8T淋巴细胞的杀伤活性,同时,检测CD8T淋巴细胞培养上清液中TNF-β水平。分别采用生物学活性法和ELISA测定瘢痕患者和正常对照IFN-γ和IL-4分泌水平。结果：不同组别CD8T细胞亚群比例比较结果和CD4T细胞相似,即在对照组和轻度瘢痕组,中度瘢痕组和重度瘢痕组差异不具有显著性,其余各组间差异具有显著性。血清中I FN-γ在各组间差异均具有显著性;上述各组血清中I L-4表达水平除在轻度和中度瘢痕组间差异不具有显著性外,其它各组间差异均具有统计学意义。CD8T淋巴细胞杀伤效应在效靶比为5：1时,除轻度瘢痕和中度瘢痕组间差异不具有显著性外,其余各组间差异均具有统计学意义。CD8T细胞培养上清中TNF-β水平在各组间差异均具有显著性。结论：同对照组比较,瘢痕患者适应性免疫出现以细胞免疫功能升高,伴随体液免疫功能降低的趋势,并且随着瘢痕程度的加重,这种变化渐趋明显。提示,瘢痕组织的形成可能与机体细胞免疫功能异常升高和体液免疫功能水平降低有关。     

Naturally occurring prostate cancer antigen-specific T cell responses of a Th1 phenotype can be detected in patients with prostate cancer

BACKGROUND: Cytotoxic T cells (CTL) are considered one of the primary effector cell populations in antitumor immunity. Recent studies, however, have demonstrated the critical importance of helper T cells (Th), specifically interferon gamma (IFN gamma)-secreting Th1 cells, either by supporting an appropriate CTL environment or by recruiting other effector cells. We evaluated whether patients with prostate cancer have naturally occurring Th-cell responses specific for two prostate cancer-associated antigens, prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP), and whether Th1-type responses to these antigens could be detected. METHODS: Peripheral blood mononuclear cells (PBMC) were collected from 80 patients with prostate cancer and 20 male controls without prostate disease. Th-cell responses were evaluated by measuring antigen-specific proliferation. IFN gamma and IL-5 secretion in response to antigen stimulation was determined by enzyme-linked immunosorbent assay. RESULTS: T cell proliferative responses specific for PSA and PAP could be detected in patients with prostate cancer. Six percent (5/80) of patients had T cell responses specific for PSA and 11% (9/80) for PAP. T cell responses specific for PSA were more prevalent in patients with metastatic disease (P = 0.02), whereas responses specific for PAP could be detected in patients irrespective of disease stage. IFN gamma-producing Th cells, specific for both PSA and PAP, could be identified in patients with prostate cancer. CONCLUSIONS: Patients with prostate cancer can have detectable Th-cell responses specific for the prostate cancer-associated proteins PSA and PAP. The presence of antigen-specific Th1 immune responses in prostate cancer patients suggests that an immune environment capable of supporting antigen-specific CTL may exist in vivo. Prostate 47:222-229, 2001.     

Combined treatment with triptolide and rapamycin prolongs graft survival in a mouse model of cardiac transplantation.

Current immunosuppressive strategies for transplantation have failed to achieve long-term graft survival. In this study, we investigate the effects of combined treatment with triptolide (TPT) and rapamycin (Rapa) on graft survival as well as changes in pathology and immunological responses. Heterotopic heart transplantation was performed. TPT and Rapa were administered either alone or in combination. The mean survival time (MST) for the cardiac allografts in animals receiving the combination of TPT and Rapa was 93.5 +/- 6.7 days compared to treatment with TPT (MST: 23.5 +/- 5.3 days), Rapa (22 +/- 1.3 days) alone or no treatment (7.66 +/- 0.8 days). Histopathological evaluation showed that inflammatory cell infiltration was markedly reduced in grafts with combined treatment groups. Down-regulation of CCL19, CCR5, CCR7, interferon gamma and interleukin (IL)-12 in the combination treatment was accompanied by increased expression of IL-4, IL-10 and CD4(+)CD25(+)Foxp3(+) regulatory T (Tr) cells in spleen. Finally, dendritic cell (DC) maturation was impaired by treatment with TPT/Rapa. Our results demonstrate that combination therapy with TPT and Rapa markedly prolongs cardiac allograft survival. This effect is accompanied by inhibition of DCs maturation, conditioning DCs to adopt tolerogenic phenotype, and the expansion of Tr cells. These results add weight to the application of combination therapy in transplantation.     

Inflammatory pathway employed by Red Maca to treat induced benign prostatic hyperplasia in rats

Benign prostatic hyperplasia (BPH) is a pathology characterised by an increase in prostate size associated with low urinary tract symptoms. Finasteride (F), a 5a-reductase inhibitor, is the standard treatment for BPH reducing prostate weight but also sexual desire. The Peruvian plant known as Red Maca (RM) (Lepidium meyenii) inhibits BPH in rats and mice. The aim of the study was to assess the inflammatory effect of RM and finasteride in rats with testosterone enanthate (TE)-induced BPH. Thirty rats were divided into 5 groups: Control, TE (50 mg/rat), TE + F (0.6 mg/kg), and two groups of TE + RM 40/80 (40 or 80 mg). After treatments, tumour necrosis factor alpha (TNFa), interleukin 4 (IL4) and interferon gamma (INFg) as well as testosterone and oestradiol were evaluated and inflammatory cells (neutrophils, mast cells and lymphocytes) in prostate were quantified. Red Maca and finasteride treatments decreased inflammatory cells counts in prostate, inhibiting TNFa by different pathways. Finasteride increased IL4 whereas Red Maca increased INFg. In conclusion, data suggest that finasteride acts on Th2 response by increasing IL4 in prostate, while Red Maca acts on Th1 response mediated by INFg.