Development and proliferation of lymphocytes in mice deficient for both interleukins-2 and -4

Interleukin (IL)-2 and IL-4 are considered as important regulators of growth and differentiation of lymphocytes. We report that in mice made deficient for both IL-2 and IL-4 by gene targeting all major T cell subsets and B cells were normal, indicating that IL-2 and IL-4 are not essential for development of the immune system. Paradoxically, proliferation of T cells was increased in both IL-2- and IL-4-deficient homozygous mice.     

精神分裂症患者致炎性细胞因子和酪氨酸羟化酶mRNA表达水平的研究

目的探讨精神分裂症的外周神经免疫机制及其与临床症状的关系。方法检测精神分裂症患者致炎性细胞因子白介素-1β（IL-1β）、肿瘤坏死因子-α（TNF—α）以及酪氨酸羟化酶（TH）的mRNA表达水平，采用逆转录-聚合酶链反应及半定量检测技术，分别检测39例精神分裂症患者（患者组）、25例同胞（同胞组）及30名正常对照（对照组）外周血单个核细胞（PBMC）IL-1β、TNF-α及TH基因表达水平，同时应用阳性和阴性症状量表（PANSS）评定精神分裂症患者临床症状。结果患者组、同胞组及对照组IL-1β的mRNA表达水平分别为1．52±1．01、1．52±1．09和0．74±0．38；TNF—α的mRNA表达水平分别为1．18±0．99、1．01±0．87和0．70±0．29；TH的mRNA表达水平分别为0．55±0．33、0．61±0．32和0．28±0．20。患者组和同胞组的IL-1β、TNF—α、TH的mRNA表达水平均明显高于对照组（P〈0．05或P〈0．01）。患者组IL-1β（r=0．420）、TNF—α（r=0．430）的mRNA表达水平与PANSS的-般病理症状分呈正相关（P〈0．01）。同胞组与对照组合并统计，IL-1β与TNF-α的mRNA表达水平呈正相关（r=0．847，P〈0．01）；IL-1β与TH的mRNA表达水平呈正相关（r=0．666，P〈0．01）。患者组仅IL-1β与TNF—α的mRNA表达水平呈正相关（r=0．942，P〈0．01）。结论精神分裂症患者PBMC细胞TH、IL-1β和TNF—α的mRNA表达水平高于正常，且与精神分裂症的-般病理症状显著相关。     

休克期切痂对烫伤大鼠全身和肠道局部免疫功能的影响

目的　观察休克期切痂对烫伤大鼠全身和肠道局部免疫功能的影响 ,探讨其可能的机制。　方法　选用 96只Wistar大鼠。取其中 2 4只大鼠的躯干部皮肤冻存于液氮中 ,另取 8只作正常对照组。余下 6 4只造成 30 %TBSAⅢ度烫伤后 ,随机分为A组 2 4只 ,伤后不作任何处理 ;B组 2 4只 ,伤后 2 4h腹腔注射等渗盐水 5 0ml/kg,一次性切痂后用上述冻存异体皮覆盖 ;C组 1 6只 ,伤后 72h进行处理 ,方法同B组。检测A、B组大鼠伤后 2、4、8d和C组伤后 4、8d及正常对照组大鼠的脾淋巴细胞增殖功能、血浆和肠组织白细胞介素 (IL)2水平、肠黏液分泌型免疫球蛋白A(sIgA)及肠组织中二胺氧化酶 (DAO)含量的变化。　结果　各时相点下A、B、C组大鼠脾淋巴细胞增殖功能、血浆IL 2水平、肠组织IL 2及肠黏液sIgA含量均较正常对照组减少。B组伤后 4、8d和C组伤后 8d的脾淋巴细胞增殖功能接近正常对照组 ,血浆和肠组织IL 2水平明显高于A组 (P <0.0 1)。伤后 4、8d,B组肠黏液sIgA含量分别为 (3.5 1± 2 .1 4 )、(3.0 3± 0 .95 )mg/g,C组分别为 (1 .4 0± 0 .6 4 )、(1 .5 2± 1 .2 6 )mg/g,B组较C组增加近 1倍 (P 0.0 1 )。A组伤后 4、8d肠组织DAO活性低于正常对照组和B组 (P 0.0 5)。结论　休克期切痂有助于烫伤大鼠全身和肠道     

Differential effects of IL-1ra on sickness behavior and weight loss induced by IL-1 in rats

Peripheral and central injections of recombinant human interleukin-1β (IL-1β) have been shown to decrease social exploration and to induce body weight loss in rats. To characterize the receptor mechanisms of these effects, we used as a tool a specific antagonist of the receptors of IL-1, IL-1ra. Intraperitoneal (i.p.) administration of IL-1ra (8 mg/kg) blocked the effect of i.p. injection of IL-1β (4 μg/rat) on social behaviour but not on body weight. Central administration of IL-1ra (60 μg/rat, i.c.v.) abrogated the effects of centrally administered IL-1β (30 ngn/rat, i.c.v.) on both social behaviour and body weight. Central injection of IL-1ra (4 μg/rat, i.c.v.) also attenuated the effects of i.p. administered IL-1β (4 μg/rat) on social behaviour but not on body weight. These results suggest that the effects of IL-1β on social behavior are mediated centrally and that its effect on the loss of body weight involves different receptor mechanisms.     

Inhibition of tissue factor surface expression in human peripheral blood monocytes exposed to cytokines

Interleukin (IL)-4, IL-10, IL-13 and transforming growth factor beta (TGF-β) are known to regulate several monocyte functions, including inhibition of the synthesis of different cytokines. Using quantitative RT-PCR and flow cytometry analysis we investigated the effects of these cytokines on bacterial lipopolysaccharide (LPS)-induced tissue factor (TF) expression in human monocytes. The effects of IL-4 and IL-10 on monocyte chemoattractant protein-1 (MCP-1)- and C-reactive protein (CRP)-induced TF expression were also studied. A direct comparison revealed that IL-4, IL-10 and IL-13 all down-regulated LPS-induced TF expression in a concentration-dependent manner without the need for priming. In contrast, TGF-β required 4 h of priming to inhibit TF expression induced by LPS. IL-10 was the most powerful inhibitor, causing almost complete inhibition at 5 ng/ml. IL-4 and IL-13 exhibited a significantly lower inhibitory capacity even at concentrations of 100 ng/ml. IL-4 and IL-10 showed similar concentration-dependent inhibition of MCP-1- and CRP-induced TF expression. We also showed that the regulatory effect of the interleukins occurred at the mRNA level. In vivo , these inhibitory cytokines may play an important regulatory role in preventing thrombosis. IL-10, in particular, may be a possible candidate as a TF-preventing drug.     

Abdominal vagotomy attenuates interleukin-1β-induced nitric oxide release in the paraventricular nucleus region in conscious rats

Nitric oxide (NO) has recently been shown to modulate the hypothalamic–pituitary–adrenal axis response to interleukin-1β (IL-1β). We measured levels of nitrite (NO₂⁻) and nitrate (NO₃⁻) in the hypothalamic paraventricular nucleus (PVN) region using an in vivo brain microdialysis technique in conscious rats. Intraperitoneally administered IL-1β produced a significant increase in both NO₂⁻ and NO₃⁻ levels in the PVN region. We also examined the possible involvement of the abdominal vagal afferent nerves in this effect. In abdominal-vagotomized rats, the increase was significantly attenuated compared to that in sham-operated rats. Our results suggest that the abdominal vagal afferent nerves are involved in intraperitoneally administered IL-1β-induced NO release in the PVN region.     

IL-17A对卵巢癌进展的影响及机制研究

目的:采用动物实验和临床标本探讨白细胞介素-17A（IL-17A）对卵巢癌（OvCa）进展的影响,并探索相应机制。方法:以C57BL/6遗传背景的野生型（WT）小鼠和IL-17A缺陷型（IL-17A-/-）小鼠为研究对象,原位注射相同基因背景来源的小鼠OvCa细胞系ID8构建卵巢原位种植瘤模型,观察IL-17A对小鼠OvCa生长转移的影响。应用Western印迹检测WT小鼠和IL-17A-/-小鼠肿瘤组织中信号转导和转录激活因子3（STAT3）、磷酸化STAT3（p-STAT3）、脂肪酸结合蛋白4（FABP4）表达情况,以探讨IL-17A促进OvCa进展的机制。收集OvCa患者临床病理组织切片标本,应用免疫组化分析IL-17A、FABP4表达与OvCa进展的相关性。结果:WT小鼠造模部位卵巢明显肿大,与周围组织黏连,其表面可见若干瘤结节;IL-17A-/-小鼠卵巢肿大,与周围组织无黏连,表面瘤结节较少。与WT小鼠相比,IL-17A-/-小鼠腹腔瘤结节显著减少（t=5.132,P<0.05）。Western印迹结果显示与WT小鼠相比,IL-17A-/-小鼠肿瘤组织中p-STAT3、FABP4蛋白表达显著降低（均P＜0.05）。OvCa患者临床病理标本显示IL-17A、FABP4表达与癌症FIGO分期、转移相关（均P＜0.05）,并且在OvCa患者中IL-17A与FABP4表达也具有一定相关性（P＜0.05）。结论:动物实验和临床标本证实IL-17A通过上调FABP4表达促进OvCa进展。     

酪酸梭菌活菌散对支气管哮喘患儿辅助性T细胞17、调节性T细胞及其相关细胞因子和肠道菌群的影响

目的 探讨酪酸梭菌活菌散对支气管哮喘患儿辅助性T细胞17(Th17细胞)、调节性T细胞(Tr细胞)及其相关细胞因子和肠道菌群的影响。方法 选择2018年3月至2020年6月新乡医学院第三附属医院收治的97例支气管哮喘患儿为研究对象,根据治疗方法将患儿分为观察组(n=49)和对照组(n=48)。对照组患儿给予吸入用布地奈德混悬液、吸入用异丙托溴铵溶液和孟鲁司特钠颗粒治疗;在对照组治疗基础上,观察者组患儿给予酪酸梭菌活菌散治疗,2组患儿均治疗2个月。应用流式细胞仪检测2组患儿治疗前后Th17细胞和Tr细胞水平,并计算Th17细胞与Tr细胞的比值(Th17/Tr);采用酶联免疫吸附试验检测2组患儿治疗前后血清中白细胞介素-17(IL-17)、白细胞介素-10(IL-10)水平。使用儿童肺功能仪检测2组患儿治疗前后第1秒用力呼气容积(FEV₁)、FEV₁/用力肺活量(FVC)、呼气流量峰值(PEF)日变异率;分别于治疗前后收集并培养2组患儿新鲜粪便,观察肠道菌群分布情况。治疗期间观察2组患儿不良反应发生情况,治疗后评估患儿临床疗效;所有患儿治疗后随访...     

Th17/Treg细胞免疫平衡的相关调控机制研究进展

免疫系统可识别、抵抗病原微生物及清除体内异常分裂的细胞,平衡的免疫系统对维持正常的机体反应活动至关重要。人体内的多种细胞都可参与维持免疫稳态,其中辅助性T淋巴细胞17（Th17）和调节性T淋巴细胞（Treg）发挥着重要作用,失衡的免疫系统可致多种免疫性疾病的发生。Th17/Treg细胞平衡受细胞因子、代谢、肠道微生态及翻译后修饰等多种机制调控,该文通过总结相关机制为免疫性疾病治疗提供新思路和策略。