Rv0220蛋白IFN-γ释放试验对结核潜伏感染的诊断价值研究

目的 探讨Rv0220蛋白γ-干扰素(IFN-γ)释放试验(IGRA)在结核分枝杆菌(Mycobacterium tuberculosis, MTB)潜伏性感染中的诊断价值。方法 使用目前IGRA广泛使用的ESAT-6、CFP-10、TB7.7三种刺激抗原作为参照,用Rv0220蛋白刺激112例新疆喀什结核病防治中心(肺核医院)健康体检外周血样本,分析Rv0220蛋白在IGRA时检测结核潜伏性感染的灵敏性与特异性。结果 Rv0220蛋白在刺激IFN-γ释放水平上与ESAT-6、CFP-10、TB7.7混合抗原刺激无显著性差异,以ESAT-6、CFP-10、TB7.7混合抗原检测结果为参照,Rv0220的蛋白检测临床样本的灵敏性与特异性分别为72.73%、100%,阳性预测值为72.73%,阴性预测值为40%。结论 Rv0220抗原蛋白在人结核病外周血IFN-γ体外释放实验中可作为刺激原,对于结核潜伏性感染具有较高的诊断价值。     

氯诺昔康超前镇痛对胃癌根治术患者血清IL-2、IL-10、sIL-2R的影响

目的观察氯诺昔康超前镇痛对胃癌根治术患者血清IL-2、IL-10、sIL-2R的影响,并探讨其临床意义。方法将45例择期行胃癌根治术患者随机分为3组,Ⅰ组术后以曲马多行自控静脉镇痛（PCIA）;Ⅱ组以氯诺昔康行PCIA;Ⅲ组在麻醉前和关腹时静推氯诺昔康8 mg,术后以曲马多行PCIA。分别于PCIA后8、12、24、48、72 h采用视觉模拟评分（VAS）判定镇痛效果,分别于麻醉前（T1）、切皮后90 min（T2）及术后24（T3）、48（T4）、72 h（T5）测定血清IL-2、IL-10、sIL-2R。结果三组PCIA后各时点VAS比较,P均〉0.05。三组血清IL-2从T2起均较T1显著下降（P均〈0.05）;血清IL-10从T3起均较T1显著升高（P均〈0.05）,Ⅰ、Ⅲ组T5时仍显著高于T1水平（P均〈0.05）,Ⅱ组则恢复至T1水平（P〉0.05）,与Ⅰ、Ⅲ组值相比较P均〈0.05;Ⅰ、Ⅱ组血清sIL-2R从T3起均较T1明显升高（P均〈0.05）,Ⅲ组此时与T1相比,P〉0.05,但明显低于Ⅰ、Ⅱ组（P均〈0.05）,T5时与T1相比,P〈0.05。结论氯诺昔康超前镇痛能降低胃癌根治术后患者血清IL-2、IL-10、sIL-2R水平,从而减少手术对机体免疫的影响,且不影响镇痛效果。     

聚乙二醇干扰素α-2b治疗慢性乙型肝炎患者外周血T淋巴细胞亚群和血清细胞因子水平变化*

目的 研究聚乙二醇干扰素α-2b治疗慢性乙型肝炎患者外周血T淋巴细胞亚群和血清细胞因子水平的变化。 方法 2014年1月~2016年1月我院收治的184例慢性乙型肝炎患者,92例接受聚乙二醇干扰素α-2b联合恩替卡韦治疗48 w,另92例只接受恩替卡韦治疗。使用流式细胞仪检测外周血T淋巴细胞亚群,采用放射免疫法检测血清IL-6、INF-ɑ、IL-4,采用酶联免疫吸附法检测血清IL-17、TGF-β1和HBV标记物,采用荧光定量PCR法检测血清HBV DNA、核转录因子RORγt、Foxp3、IL-17mRNA。 结果 在停药随访24 w,联合组与恩替卡韦组血清HBV DNA阴转率分别为86.96%和84.78%（P>0.05）;联合组血清HBeAg阴转率为28.89%（13/45）,与恩替卡韦组的15.22%（7/46）比,无显著性差异（P>0.05）;联合组血清ALT水平为（34.6±11.6） U/L,显著低于恩替卡韦组【（64.6±20.5） U/L,P<0.05】;联合组外周血CD3+、CD4+细胞和CD4+/CD8+比值分别为（75.6±14.5）%、（42.7±10.3）%和（1.4±0.6）,显著高于恩替卡韦组【（66.8±14.4）%、（36.7±8.5）%和（1.0±0.5）,P<0.05】,CD8+细胞百分比为（29.3±7.3） %,显著低于恩替卡韦组【（34.8±8.5） %,P<0.05】,两组NK细胞百分比比较无显著性差异（P>0.05）;治疗前两组血清IL-6、IL-17、IL-4、INF-ɑ、TGF-β1水平比较无显著性差异（P>0.05）,治疗后联合组血清IL-6水平为（6.8±1.2）pg/ml,显著高于恩替卡韦组【（3.5±0.8） pg/ml,P<0.05】,IL-17水平为（0.7±0.3） pg/ml,显著低于恩替卡韦组【（2.8±0.9） pg/ml,P<0.05】,IL-4水平为（1.4±0.5）pg/ml,显著低于恩替卡韦组【（3.8±1.5）pg/ml,P<0.05】,INF-ɑ水平为（4.0±1.3） pg/ml,显著高于恩替卡韦组【（2.6±0.9）pg/ml,P<0.05】,两组血清TGF-β1水平比较无显著性差异（P>0.05）;治疗前两组血清Foxp3、IL-17和RORγt mRNA水平比较无显著性差异（P>0.05）,治疗后联合组血清RORγt水平为（0.86±0.31）,显著低于恩替卡韦组【（1.56±0.43）,P>0.05】,而两组血清Foxp3和IL-17mRNA水平比较无显著性差异（P>0.05）。 结论 聚乙二醇干扰素α-2b能通过调控细胞因子和核转录因子水平,从多个环节调控慢性乙型肝炎患者免疫功能,发挥抗病毒作用。     

γ-干扰素联合抗结核药物治疗肺结核临床疗效的Meta分析

目的:系统评价γ-干扰素(IFN-γ)联合抗结核药物治疗肺结核的临床疗效和安全性,为IFN-γ在肺结核临床治疗中的应用提供依据。方法:检索PubMed、Embase、中国生物医学文献数据库、中国知网、万方数据库,纳入自建库以来至2022年3月1日公开发表的IFN-γ联合抗结核药物治疗肺结核的临床随机对照试验(RCT)研究。根据Cochrane手册,应用Review Manager 5.4 软件对纳入文献进行质量评价。应用STATA 12.0 软件对IFN-γ联合抗结核药物治疗组(观察组)和单纯抗结核药物治疗组(对照组)肺结核患者治疗2~3个月及6~9个月后痰菌阴转率、病灶吸收率、空洞闭合率及两组不良反应发生率,以及治疗后外周血CD4⁺T细胞、CD8⁺T细胞百分比的差异进行评价。结果:共纳入18篇文献,共计1341例患者。Meta分析结果显示,与对照组比较,观察组患者治疗2~3个月和6~9个月后,痰菌阴转率RR(95%CI)值分别为1.40(1.26~1.56)和1.41(1.12~1.76);病灶吸收率RR(95%CI)值分别为1.43(1.09~1.88)和2.84(1.65~5.00);空洞闭合率RR(95%CI)值分别为2.07(1.47~2.92)和1.56(1.28~1.91),均显著高于对照组(P值均<0.05)。此外,与对照组比较,治疗后观察组外周血CD4⁺T细胞百分比升高更明显、CD8⁺T细胞百分比降低更明显(P值均<0.05), 加权均数差(WMD;95%CI)分别为5.18(2.53~7.84)和-3.16(-6.08~-0.23)。与对照组比较,观察组不良反应发生率RR(95%CI)值为1.06(0.70~1.60),其中,肝功能异常发生率、皮肤过敏反应发生率、胃肠道不良反应发生率RR(95%CI)值分别为1.02(0.95~1.11)、1.03(0.95~1.11)和1.01(0.93~1.11),差异均无统计学意义(P值均>0.05)。结论:IFN-γ联合抗结核药物治疗肺结核,可以促进患者病灶吸收、痰菌阴转率,且能改善肺结核患者的免疫指标。     

慢性乙型肝炎和肝硬化患者血清TLR4、TGF-β1和IL-17水平及其临床意义*

目的 分析慢性乙型肝炎（CHB）和乙型肝炎肝硬化患者血清Toll样受体4（TLR4）、转化生长因子-β1（TGF-β1）和白细胞介素-17（IL-17）水平变化及其临床意义。方法 2015年6月~2017年4月本院收治的112例CHB、52例乙型肝炎肝硬化患者和选择的33例健康人,采用ELISA法检验血清IL-17、TLR4、TGF-β1水平,常规进行肝活检。结果 慢性乙型肝炎、肝硬化和健康人血清IL-17水平分别为（264.42±32.53） pg/ml、（271.54±33.71） pg/ml和（64.18±5.52） ng/ml,血清TLR4水平分别为（5.81±0.83） pg/ml、（37.41±6.05） pg/ml和（1.07±0.13）ng/ml,血清TGF-β1水平分别为（3.67±0.42） pg/ml、（7.82±1.07） pg/ml和（1.61±0.07） ng/ml,差异明显（P<0.05）;19例Child-Pugh B级血清IL-17、TLR4和TGF-β1水平分别为（231.38±28.67） pg/ml、（18.61±2.87） pg/ml和（5.76±0.52） ng/ml,16例C级患者分别为（301.72±32.72） pg/ml、（39.47±6.82） pg/ml和（9.42±1.27） ng/ml,均明显高于17例Child-Pugh A级患者【分别为（204.53±26.57） pg/ml、（4.72±0.71） pg/ml和（3.18±0.34） ng/ml,P<0.05】;肝活检组织学检查发现S0 8例、S1 42例、S2 43例、S3 19例、S4 52例,血清IL-17、TLR4、TGF-β1水平随着肝组织纤维化分期严重而升高。结论 乙型肝炎肝硬化患者血清TLR4、TGF-β1和IL-17水平升高,对诊断和指导治疗可能有帮助。     

IFN-α1b治疗对慢性乙肝患者血清IL-1、SIL-2R和IFN-γ水平的影响

目的　探讨α 干扰素 (INF α 1b)治疗慢性乙型肝炎细胞免疫机制。方法　收集IFN α 1b治疗慢性乙型肝炎患者 3 0例 ,分别在治疗前、治疗后 1个月、3个月、6个月和 9个月留取血清标本 ,用MTT法检测血清白细胞介素 1(IL 1)水平 ,用ELISA法检测血清可溶性白细胞介素 2受体 (sIL 2R)和γ 干扰素 (INF γ)水平 ,并与 3 0例健康献血员作对照。结果　与正常对照组相比 ,慢性乙型肝炎患者血清sIL 2R水平升高 (P <0 0 5 ) ,经IFN α治疗后 ,血清IL 1、sIL 2R明显升高 (P <0 0 1)。结论　IFN α 1b调节体内细胞因子变化 ,参与细胞免疫调节。     

2H3R3E3Z3/4H3R3方案引起的药物性肝炎及其对抗结核效果的影响

目的　观察和研究2H₃R₃E₃Z₃/4H₃R₃治疗初治涂阳病人药物性肝炎的发生率和药物性肝炎对抗结核效果的影响。方法 对肝功正常、应用2H₃R₃E₃Z₃/4H₃R₃治疗的初治涂阳病人每月复查1次肝功,复查出现ALT升高的每周复查1次肝功,疗程完成后考核疗效。结果 （1）药物性肝炎发生率为23.1%,其中有基础性肝病患者药物性肝炎发生率为66.3%;（2）抗结核过程中肝功检查第1次发现ALT在50 U/L～100 U/L,且无明显肝损症状和胆红素增高者,有51.2%的患者属于一过性转氨酶升高;（3）73.2%的药物性肝炎发生在抗结核治疗的前2个月,26.8%的药物性肝炎发生在抗结核治疗的后4个月;（4）无因药物性肝炎而死亡的病例,药物性肝炎患者停用抗结核药物并行护肝等治疗后肝功恢复时间平均为2.3周,其中,有基础性肝病者肝功恢复时间平均为3.9周,无基础性肝病者肝功恢复时间平均为1.8周;（5）总的肺结核治愈率为94.6%,未发生药物性肝炎患者肺结核治愈率为97.0%,发生药物性肝炎患者肺结核治愈率为86.6%,有基础性肝病患者肺结核治愈率为78.6%。结论 （1）药物性肝炎是影响肺结核,尤其是影响有基础性肝病患者肺结核治疗效果的重要因素,2H₃R₃E₃Z₃/4H₃R₃不宜广泛应用于HBsAg（+）等有基础性肝病的初治涂阳肺结核病人;（2）抗结核过程中肝功检查第1次发现ALT在50 U/L～100 U/L,且无明显肝损症状和胆红素增高者,有51.2%的病例属于一过性转氨酶升高,只要加强护肝治疗,可以不停抗结核药物,但应密切观察患者反应和肝功变化;（3）药物性肝炎虽然全疗程中均可出现,但主要发生在强化期,故应注重强化期的护肝治疗和肝功监测。     

囊虫病患者血清sIL-2R、TNFα、IL-6和IL-8治疗前后的

细胞因子参与多种感染性疾病的变态反应和免疫反应 ,已越来越被人们所重视。寄生虫所致的感染 ,其可溶性白细胞介素 2受体 (ｓＩＬ 2Ｒ)、肿瘤坏死因子 α(ＴＮＦα)、白细胞介素 6 (ＩＬ 6 )和白细胞介素 8(ＩＬ 8)水平及动态改变国内报道甚少。为此 ,我们对 48例囊虫病患者的血清ｓＩＬ 2Ｒ、ＴＮＦα、ＩＬ 6和ＩＬ 8在治疗前后的变化进行了测定 ,并初步探讨其临床意义。材料和方法一、研究对象48例均为本院感染内科住院患者 ,年龄 14～ 6 7岁 ,男31例 ,女 17例。 48例均行头颅ＣＴ或ＭＲＩ检查 ,个别患者经皮肤活检病理证实。其中单…     

胆宁片联合瑞舒伐他汀治疗非酒精性脂肪性肝病患者HOMA-IR和血清TNF-α水平变化*

目的 探讨胆宁片联合瑞舒伐他汀对非酒精性脂肪性肝病（NAFLD）患者的治疗效果及其对血清肿瘤坏死因子α（TNF-α）和胰岛素抵抗指数（HOMA-IR）的影响。方法 2015年9月~2016年9月我院就诊的NAFLD患者150例,随机将其分成观察组和对照组各75例。给予观察组患者瑞舒伐他汀联合胆宁片治疗,给予对照组患者瑞舒伐他汀治疗,两组均治疗6个月。采用酶联免疫吸附法检测TNF-α水平,常规检测空腹血糖和胰岛素水平,并计算HOMA-IR。结果 治疗前,两组患者血生化指标无明显差异（P>0.05）;治疗后,观察组血清谷丙转氨酶（ALT）和谷草转氨酶（AST）水平分别为（46.92±10.21） U/L和（65.39±9.86） U/L,显著低于对照组的【（70.74±12.93） U/L和（99.21±10.97） U/L,P<0.05】;治疗前,两组血清TNF-α和HOMA-IR比较无明显差异（P>0.05）;治疗后,观察组患者血清TNF-α和HOMA-IR分别为（3.44±1.26） μg/L和（1.87±0.84）,显著低于对照组的【（4.08±1.29）μg/L） 和（2.26±0.74）,P<0.05】。结论 胆宁片联合瑞舒伐他汀治疗NAFLD患者能明显改善肝功能,并能降低血清TNF-α和HOMA-IR水平,临床效果显著。     

各型乙型肝炎患者血清sIL-2R、IFN-γ和IL-1变化的研究

目的：探讨各型乙型肝炎患者血清ｓＩＬ－２Ｒ、ＩＦＮ－γ和ＩＬ－１变化及其临床意义。方法：收集急性肝炎、慢性肝炎、慢性重型肝炎和活动性肝硬变患者血清标本各１６例,１６健康人血清标本作为正常对照组,采用酶联免疫吸附试验（ＥＩＦＳＡ）检测各型乙型肝炎患者血清中ｓＩＬ－２Ｒ和ＩＦＮ－γ水平,采用ＭＴＴ法检测各型乙型肝炎患者血清中ＩＬ－１水平,并与正常对照组进行比较。结果：急性肝炎患者血清ｓＩＬ－２Ｒ、ＩＦ     

Hyperresponsive febrile reactions to interleukin (IL) 1α and IL-1β, and altered brain cytokine mRNA and serum cytokine levels, in IL-1β-deficient mice

IL-1β is an endogenous pyrogen that is induced during systemic lipopolysaccharide (LPS)- or IL-1-induced fever. We have examined the fever and cytokine responses following i.p. injection of IL-1 agonists, IL-1α and IL-1β, and compared these with response to LPS (i.p.) in wild-type and IL-1β-deficient mice. The IL-1β deficient mice appear to have elevated body temperature but exhibit a normal circadian temperature cycle. Exogenously injected IL-1β, IL-1α, or LPS induced hyperresponsive fevers in the IL-1β-deficient mice. We also observed phenotypic differences between wild-type and IL-1β-deficient mice in hypothalamic basal mRNA levels for IL-1α and IL-6, but not for IL-1β-converting enzyme or IL-1 receptor type I or type II. The IL-1α mRNA levels were down-regulated, whereas the IL-6 mRNA levels were up-regulated in the hypothalamus of IL-1β-deficient mice as compared with wild-type mice. The IL-1β-deficient mice also responded to LPS challenge with significantly higher serum corticosterone and with lower serum tumor necrosis factor type α levels than the wild-type mice. The data suggest that, in the redundant cascade of proinflammatory cytokines, IL-1β plays an important but not obligatory role in fever induction by LPS or IL-1α, as well as in the induction of serum tumor necrosis factor type α and corticosterone responses either by LPS or by IL-1α or IL-1β.     

Higher cytotoxic activity and increased levels of IL-1β, IL-6, and TNF-α in patients undergoing cardiopulmonary bypass

Extracorporeal circulation (EC) by surgical bypass is often associated with a systemic inflammatory response. The purpose of this study was to assess the effect of EC on the serum levels of pro-inflammatory mediators Interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and soluble CD-23. Peripheral blood lymphocyte subsets and natural killer cell (NK) cytotoxic activity were also analyzed before and after the bypass process. The results from eight patients who underwent cardiac surgery showed a significant increase in the levels of IL-1β, IL-6, and TNF-α, a decrease in CD4⁺/CD8⁺ lymphocyte ratio, and an overstimulated NK cytotoxic activity. These changes on serum cytokine levels and cellular immunology parameters could play an important role in the development of adverse effects associated with EC. © 1995 Wiley-Liss, Inc.     

Cytolytic and IFN-γ-producing activities of γδ T cells in the mouse intestinal epithelium are T cell receptor-β-chain dependent

We analyzed the cytolytic activity of intraepithelial T cells (IEL) isolated from the small intestines of 2- to 3-month-old mutant mice rendered deficient in different gene(s) in which the number of IEL expressing either T cell receptor (TCR)-alpha beta (alpha beta-IEL) or TCR-gamma delta (gamma delta-IEL) were absent or markedly diminished. When compared with wild-type littermates, cytolytic activity of gamma delta-IEL was sharply attenuated in TCR-beta mutant mice but remained unaltered in TCR-alpha mutant mice in which a minor population of dull TCR-beta+ (betadim)-IEL was also present. Cytolytic activity of gamma delta-IEL was maintained in mice doubly homozygous for beta2-microglobulin and transporter associated with antigen processing 1 gene mutations in which a conspicuous decrease was noted in absolute numbers of alpha beta-IEL. In contrast, both TCR-delta and IL-7 receptor-alpha gene mutations that lead to lack of gamma delta-IEL generation did not affect the development or cytolytic activity of the remaining alpha beta-IEL. The anti-CD3 and anti-TCR-gamma delta mAb-induced IFN-gamma production of gamma delta-IEL showed the same TCR-alpha and TCR-beta mutation-dependent variability. These results indicate that cytolytic and IFN-gamma-producing activities of gamma delta T cells in mouse intestinal epithelium are TCR-beta-chain-dependent.     

Serum levels of IL-10, IL-6, IL-1ra, and sIL-2R in patients with psoriatic arthritis

Our objective was to evaluate the levels of interleukin-6 (IL-6), soluble receptors of IL-2 (sIL-2R), IL-10, and IL-1 receptor antagonists (IL-1ra) in the serum of patients with psoriatic arthritis (PsA) and to assess the correlation between these levels and parameters of clinical activity of skin and joint disease. In total, 34 patients with PsA and ten healthy volunteers participated in the study. Assessment of joint disease included duration of morning stiffness, number of tender and swollen joints, right and left grip, the presence of inflammatory spinal back pain, and Schober test. Current severity of skin disease was graded according to the psoriasis area and severity index (PASI). Erythrocyte sedimentation rate (ESR) was determined as a marker of disease activity. Serum levels of IL-6, sIL-2R, IL-1ra, and IL-10 were measured by an enzyme immunoassay kit. Significantly higher serum levels of IL-6, sIL-2R, IL-1ra, and IL-10 were found in patients with PsA in comparison with healthy volunteers. A statistically significant correlation was found between levels of sIL-2R and PASI, whereas no association was found with clinical parameters of joint severity. Levels of IL-1ra correlated with the number of tender and swollen joints. No correlation was found between levels of IL-6, IL-10, and clinical parameters of skin and joint severity. In the group of patients with PsA, serum levels of sIL-2R clearly correlated with severity of skin disease, whereas levels of IL-1ra were associated with joint severity. Received: 18 June 1999 / Accepted: 1 October 1999     

IFN-γ and TNF-α secretion by CD4+ and CD8+ TCRαβ+ T-cell clones derived early after allogeneic bone marrow transplantation

Abstract: Secretion of the potentially antileukaemic cytokines IFN-γ and TNF-α was investigated for CD4 ⁺ and CD8 ⁺ TCRαβ⁺ T-cell clones derived from 4 leukaemia patients 3–6 weeks after allogeneic BMT. We investigated cytokine secretion in response to the activation signal accessory cells + phytohaemagglutinin + Interleukin 2. All clones derived after BMT were capable of IFN-γ and TNF-α secretion, and both for CD4⁺ (n = 96) and CD8⁺ (n = 8) T cells quantities of IFN-γ and TNF-α were significantly correlated with one another. When comparing the overall results for posttransplant and normal T-cell clones derived from 2 bone marrow donors (n = 65), both CD4⁺ and CD8⁺ TCRαβ⁺ T-cell clones showed increased IFN-γ production, and CD4⁺ but not CD8⁺ clones showed a decreased TNF-α secretion. The results suggest that noncytotoxic T cells derived after allogeneic BMT can produce IFN-γ and TNF-α and may thus be capable of mediating antileukaemic effects.     

TNF-α, IL-8, soluble ICAM-1, and neutrophils in sputum of cystic fibrosis patients

The cytokines tumor necrosis factor-α (TNF-α), interleukin-8 (IL-8), and intercellular adhesion molecule-1 (ICAM-1) have important roles in regulating neutrophil migration and the inflammatory response. To determine whether the concentration of these cytokines and soluble ICAM-1 (sICAM-1) in sputum was increased in patients with cystic fibrosis during acute exacerbations, we conducted (1) a cross-sectional study of 40 patients, 22 who were clinically well and 18 with acute pulmonary exacerbations; and (2) an 11 months longitudinal study of 16 patients. Significant differences in clinical scores, pulmonary function, and sputum neutrophil density were found between the acutely ill and the well group. There was a strong linear relationship (P < 0.0005) between TNF-α and IL-8 concentrations in sputum, but no association between clinical status and cytokine concentrations. The concentration of sICAM-1 was lower in acutely ill compared with well patients in the cross-sectional study. Recovery of exogenous IL-8 added to sputum was complete, while recovery of TNF-α averaged 70%. Recovery of exogenous sICAM-1 was only 43%, and the recoveries were lower in sputum samples from acutely ill patients than those from stable patients (P = 0.018). These data indicate that in cystic fibrosis patients, sputum concentrations of TNF-α and IL-8 are not increased during acute exacerbations of pulmonary inflammation. Pediatr Pulmonol. 1996; 21:11–19 . © 1996 Wiley-Liss, Inc.     

Evaluation of cytokine polymorphisms (TNFα, IFNγ and IL-10) in Down patients with coeliac disease

BACKGROUND: In Down syndrome there is an increased prevalence of coeliac disease, but the reasons for this association are yet unknown. AIMS: To evaluate a possible correlation between TNFalpha, IFNgamma and IL-10 genotype polymorphisms with the susceptibility to coeliac disease in Down syndrome patients. METHODS: Single nucleotide polymorphisms of TNFalpha (-308G-->A promoter region), IFNgamma (+874T-->A promoter region) and IL-10 (-1082G-->A promoter region) have been studied in 10 Down patients with coeliac disease, in 40 Down patients without coeliac disease and in 220 healthy controls. Clinical features were also studied in coeliac disease-Down syndrome patients. RESULTS: The 10 coeliac disease-Down syndrome patients had a biopsy proven coeliac disease afterward a serological testing positive to antigliadin, antiendomysium and antitransglutaminase antibodies. Intestinal biopsy showed total atrophy in 6/10 and partial villous atrophy in 4/10 of them. All coeliac disease-Down syndrome patients had silent forms of coeliac disease and classical trisomy 21. No significant differences were observed for the IFNgamma and IL-10 polymorphisms in the studied groups. A significant trend for increase of TNFalpha -308A positive frequency was observed in coeliac disease-Down syndrome patients compared to healthy controls (p=0.043). CONCLUSIONS: Single nucleotide polymorphisms of IFNgamma and IL-10 do not play a role in predisposing Down syndrome patients to coeliac disease, while the TNFalpha -308 allele could be an additional genetic risk factor for coeliac disease in trisomy 21.     

Differential Effects of Ethanol on Serum GABAergic 3α,5α/3α,5β Neuroactive Steroids in Mice,Rats, Cynomolgus Monkeys,and Humans

Background: Acute ethanol administration increases plasma and brain levels of progesterone and deoxycorticosterone‐derived neuroactive steroids (3α,5α)‐3‐hydroxypregnan‐20‐one (3α,5α‐THP) and (3α,5α)‐3,21‐dihydroxypregnan‐20‐one (3α,5α‐THDOC) in rats. However, little is known about ethanol effects on GABAergic neuroactive steroids in mice, nonhuman primates, or humans. We investigated the effects of ethanol on plasma levels of 3α,5α‐ and 3α,5β‐reduced GABAergic neuroactive steroids derived from progesterone, deoxycorticosterone, dehydroepiandrosterone, and testosterone using gas chromatography‐mass spectrometry. Methods: Serum levels of GABAergic neuroactive steroids and pregnenolone were measured in male rats, C57BL/6J and DBA/2J mice, cynomolgus monkeys, and humans following ethanol administration. Rats and mice were injected with ethanol (0.8 to 2.0 g/kg), cynomolgus monkeys received ethanol (1.5 g/kg) intragastrically, and healthy men consumed a beverage containing 0.8 g/kg ethanol. Steroids were measured after 60 minutes in all species and also after 120 minutes in monkeys and humans. Results: Ethanol administration to rats increased levels of 3α,5α‐THP, 3α,5α‐THDOC, and pregnenolone at the doses of 1.5 g/kg (+228, +134, and +860%, respectively, p < 0.001) and 2.0 g/kg (+399, +174, and +1125%, respectively, p < 0.001), but not at the dose of 0.8 g/kg. Ethanol did not alter levels of the other neuroactive steroids. In contrast, C57BL/6J mice exhibited a 27% decrease in serum 3α,5α‐THP levels (p < 0.01), while DBA/2J mice showed no significant effect of ethanol, although both mouse strains exhibited substantial increases in precursor steroids. Ethanol did not alter any of the neuroactive steroids in cynomolgus monkeys at doses comparable to those studied in rats. Finally, no effect of ethanol (0.8 g/kg) was observed in men. Conclusions: These studies show clear species differences among rats, mice, and cynomolgus monkeys in the effects of ethanol administration on circulating neuroactive steroids. Rats are unique in their pronounced elevation of GABAergic neuroactive steroids, while this effect was not observed in mice or cynomolgus monkeys at comparable ethanol doses.