IL-12和支气管哮喘

支气管哮喘是一种气道慢性炎症性疾病。越来越多的事实表明,哮喘的发生与内源性IL-12生成不足有关。IL-12无论单独应用还是作为免疫佐剂,均可逆转哮喘动物模型体内Th1/Th2失衡和抑制气道变态反应性炎症。该文综述了IL-12的生物学效应、IL-12与哮喘的关系、IL-12在哮喘治疗中的作用及其应用。     

Th22细胞与支气管哮喘

支气管哮喘是一种临床上常见的呼吸道疾病,研究发现CD4＋T细胞在哮喘的发病过程中起重要作用。Th22细胞是最近发现的一类CD4＋T细胞功能亚群之一,其主要效应因子IL-22在炎症性疾病、组织修复、创口愈合及自身免疫性疾病中起重要作用,但其具体机制尚未完全清楚。从Th22的细胞因子来源、生物学特性、分化和调控出发,简要探讨Th22细胞与哮喘之间的可能关系。     

手机辐射对孕鼠及子代IFN-γ和IL-4的影响

检测暴露于手机辐射下的孕鼠及其子代的细胞免疫因子含量水平,以探讨手机电磁辐射对孕鼠及其子代免疫功能的影响,为孕妇科学、合理使用移动通信工具提供参考。30只孕鼠随机分为Ⅰ、Ⅱ、Ⅲ、Ⅳ、Ⅴ组,每组6只,对应为空白对照组、待机对照组1、0min低强度组、30min中强度组和60min高强度组。ELISA检测孕鼠分娩24h内孕鼠及新生乳鼠外周血中IFN-γ和IL-4的含量。对Ⅰ、Ⅱ、Ⅲ、Ⅳ、Ⅴ各组母鼠外周血中IFN-γI、L-4含量进行比较,其差异无统计学意义(P>0.05);Ⅳ、Ⅴ组新生小鼠外周血中IFN-γI、L-4含量与Ⅰ、Ⅱ组比较,其差异有统计学意义(P<0.05),而且Ⅴ组新生小鼠外周血中IFN-γI、L-4含量与Ⅲ组比较,其差异也具有统计学意义(P<0.05)。手机辐射降低了胚胎期小鼠的IFN-γ和IL-4含量。     

Seasonal allergic asthma and non-specific bronchial responsiveness

Summary Bronchial responsiveness to methacoline (PD20 FEV1 mcg) was measured in 64 non smoker asthmatic patients with baseline FEV190% predicted. Patients underwent skin prick tests (SPT) and RAST.Allergic patients had: SPT3+ and RAST-score>II class to the same antigen and correlation with asthmatic symptoms; non allergic patients had negative SPT and RAST. We divided patients in four groups: 1st) allergic seasonal asthmatics before pollen season; 2nd) allergic seasonal asthmatics during pollen season; 3rd) allergic perennial asthmatics; 4th) non-allergic perennial asthmatics.A significant difference in log PD20 was observed between 1st and 2nd group (p<0.0005); between 1st and 3rd group (p<0.0005); between 1st and 4th group (p<0.0005). In allergic seasonal asthmatics before pollen season 10/20 subjects were non-responsive to methacholine (PD201600 mcg), while in 2nd, 3rd and 4th group no subjects were non-responsive.The authors conclude that non-specific bronchial hyperresponsiveness to methacoline is not constant in seasonal allergic asthmatics out of pollen season.     

吸烟对下呼吸道诱导痰中IFN-γ、IL-4、IL-5表达的影响

目的 探究吸烟对下呼吸道诱导痰中干扰素-γ（IFN-γ）、白细胞介素-4（IL-4）和白细胞介素-5（IL-5）表达的影响。方法 采用酶联免疫吸附法检测2016年3月‒2017年3月沈阳医学院附属第二医院收治的下呼吸道感染患者88例（其中吸烟者44例作为观察组,非吸烟者44例作为对照组）、健康体检者76例（其中吸烟者34例作为观察组,非吸烟者42例作为对照组）诱导痰中IFN-γ、IL-4和IL-5的表达,并对结果进行数据分析。结果 （1）健康体检者中吸烟者与非吸烟者相比,吸烟者IL-4、IL-5水平显著上升,IFN-γ水平显著下降（P<0.05）;（2）下呼吸道感染患者中吸烟者与非吸烟者相比,吸烟者IL-4、IL-5水平显著上升,INF-γ水平显著下降（P<0.05）。结论 吸烟与下呼吸道诱导痰中IL-4、IL-5和IFN-γ的水平有关,吸烟可使下呼吸道诱导痰中IL-4、IL-5水平升高而IFN-γ的水平下降。     

双歧杆菌对过敏性哮喘儿童树突状细胞分泌IL-10、IL-12等细胞因子的影响

目的探讨双歧杆菌对过敏性哮喘儿童外周血单核细胞（PBMC）来源的树突状细胞（DC）分泌IL-1β、IL-6、IL-10、IL-12、IL-23和IFN-γ的影响。方法从15例过敏性哮喘儿童和15例非哮喘儿童的外周血单个核细胞诱导生成未成熟DC,加入双歧杆菌后继续培养DC2d,用ELISA方法检测培养上清中IL-1β、IL-6、IL-10、IL-12、IL-23和IFN-γ的水平。结果双歧杆菌能明显刺激哮喘儿童DC分泌IL-12、IFN-γ,IL-1β及IL-6和非哮喘儿童DC分泌IL-12、IL-10、IL-1β及IL-23水平增高。结论双歧杆菌能够刺激过敏性哮喘儿童DC分泌IL-12和IFN-γ,可能改变Th2优势分化,纠正Th1／Th2失衡。同时双歧杆菌还能刺激哮喘儿童DC分泌IL-1p及IL-6增高,达到促进,Th17细胞分化的作用。     

Assessment of some oxidative stress parameters in patients with bronchial asthma after selenium supplementation

The goal of this study was to investigate the effect of selenium deficit replenishment in patients with bronchial asthma (BA) on manifestations of oxidative stress and conditions of the antioxidant system (AOS). The need of correction of selenium deficit in BA-patients is determined by increased requirements in antioxidants due to chronic inflammatory process responsible for pathogenesis of BA. Latvia as well as Eastern Finland, Byelorussia, some regions of Ukraine, North-Western Russia, and New Zealand belong to the endemic areas with marked selenium deficit in soils and foodstuff. Twenty patients (7 men and 13 women) with selenium deficit and verified diagnosis of BA have been examined. In addition to basic therapy all patients received organic selenium as SelenoPRECISE (PharmaNord) 200 μg daily for 16 weeks. This caused statistically significant increase of plasma selenium from 50.94 ± 7.58 to 63.59 ± 10.87 μg/l (p < 0.001), the increase of selenium-dependent glutathione peroxidase (from 38.64 ± 10.72 U/g Hb to 58.57 ± 14.64 U/g Hb, p = 0.01). Treatment of patients with selenium also normalized the parameters characterizing oxidative stress (chemiluminescence), significantly exceeded normal values before this treatment. The use of selenium in addition to basic therapy allows to abolish or reduce oxidative stress by correcting the antioxidant system.     

Vitamin D status and its modulatory effect on interferon gamma and interleukin-10 production by peripheral blood mononuclear cells in culture

ObjectivesWe aimed to investigate the influence of vitamin D on the production of the pro-inflammatory cytokine, interferon gamma (IFN-γ), and the anti-inflammatory cytokine, interleukin-10 (IL-10), in peripheral blood mononuclear cell (PBMC) cultures.MethodsThirty healthy subjects were investigated. Serum levels of calcium, 25(OH) D, and parathyroid hormone (PTH) were assessed. PBMCs were activated in-vitro by phytohemagglutinin (PHA) in the presence and absence of vitamin D3 and then levels of IFN-γ and IL-10 were determined in culture supernatant using enzyme immunoassay.ResultsSerum calcium levels were significantly lower in the vitamin D deficient group while serum PTH levels were significantly higher in the vitamin D deficient group. PTH levels were inversely correlated to both calcium and 25(OH) D levels. In culture, vitamin D inhibited IFN-γ production and increased IL-10 production by PBMCs. Serum vitamin D status had no influence on the amount of cytokine produced in culture.ConclusionsThis study demonstrates that vitamin D modulates IFN-γ and IL-10 production and provides a rationale for evaluating vitamin D as an immunomodulatory agent.     

Immunisation with a major Trypanosoma cruzi antigen promotes pro-inflammatory cytokines, nitric oxide production and increases TLR2 expression

Innate and adaptive immunity collaborate in the protection of intracellular pathogens including Trypanosoma cruzi infection. However, the parasite molecules that regulate the host immune response have not been fully identified. We previously demonstrated that the immunisation of C57BL/6 mice with cruzipain, an immunogenic T. cruzi glycoprotein, induced a strong specific T-cell response. In this study, we demonstrated that active immunisation with cruzipain was able to stimulate nitric oxide (NO) production by splenocytes. Immune cells also showed increased inducible nitric oxide synthase protein and mRNA expression. Spleen adherent cells secreted high levels of IFN-gamma and IL-12. Microbicidal activity in vitro was mainly mediated by reactive nitrogen intermediaries and IFN-gamma, as demonstrated by the inhibitory effects of NO synthase inhibitor or by IFN-gamma neutralisation. Specific T-cells were essential for NO, IFN-gamma and TNF-alpha production. Furthermore, we reported that cruzipain enhanced CD80 and major histocompatibility complex-II molecule surface expression on F4/80+ spleen cells. Interestingly, we also showed that cruzipain up-regulated toll like receptor-2 expression, not only in F4/80+ but also in total spleen cells which may be involved in the effector immune response. Our findings suggest that a single parasite antigen such as cruzipain, through adaptive immune cells and cytokines, can modulate the macrophage response not only as antigen presenting cells, but also as effector cells displaying enhanced microbicidal activity with reactive nitrogen intermediary participation. This may represent a mechanism that contributes to the immunoregulatory process during Chagas disease.     

Th 细胞因子IL-17、IFN-γ、IL-4 在狼疮性肾炎中的表达及意义

目的:探讨T辅助细胞(Th)相关细胞因子在狼疮性肾炎发病中的免疫机制作用。方法:64例系统性红斑狼疮患者和28例健康体检者作为对照,采用酶联免疫吸附测定法(ELISA法)检测所有受试者血清IL-17、IFN-γ、IL-4水平,并对其与SLEDAI、SDI、24小时尿蛋白量相关性进行研究。结果:狼疮性肾炎组血清IL-17水平显著高于狼疮无肾炎组和健康对照组(P<0.001),狼疮性肾炎组血清IFN-γ水平显著高于狼疮无肾炎组(P<0.05)和健康对照组(P<0.01),血清IL-4水平在狼疮性肾炎组、狼疮无肾炎组均显著高于健康对照组(P<0.01)。狼疮性肾炎组IFN-γ/IL-4比值显著高于狼疮无肾炎组(P<0.01)和健康对照组(P<0.05);狼疮无肾炎组IFN-γ/IL-4比值显著低于健康对照组(P<0.01)。SLE患者血清IFN-γ表达水平与SLEDAI积分呈正相关(r=0.402,P<0.05),血清IL-17、IL-4表达水平与SLEDAI、SDI、抗ds-DNA抗体、C3、24小时尿蛋白量均无相关性。结论:狼疮性肾炎患者外周血中IL-17、IFN-γ、IL-4等促炎细胞因子均有不同程度升高促起炎症发生及组织损伤,参与了狼疮性肾炎的免疫发病过程。     

Correlation of exhaled breath temperature with bronchial blood flow in asthma

In asthma elevated rates of exhaled breath temperature changes (Δe°T) and bronchial blood flow (Q_aw) may be due to increased vascularity of the airway mucosa as a result of inflammation.We investigated the relationship of Δe°T with Q_aw and airway inflammation as assessed by exhaled nitric oxide (NO). We also studied the anti-inflammatory and vasoactive effects of inhaled corticosteroid and β₂-agonist.Δe°T was confirmed to be elevated (7.27 ± 0.6 Δ°C/s) in 19 asthmatic subjects (mean age ± SEM, 40 ± 6 yr; 6 male, FEV₁ 74 ± 6 % predicted) compared to 16 normal volunteers (4.23 ± 0.41 Δ°C/s, p < 0.01) (30 ± 2 yr) and was significantly increased after salbutamol inhalation in normal subjects (7.8 ± 0.6 Δ°C/ s, p < 0.05) but not in asthmatic patients. Q_aw, measured using an acetylene dilution method was also elevated in patients with asthma compared to normal subjects (49.47 ± 2.06 and 31.56 ± 1.6 μl/ml/min p < 0.01) and correlated with exhaled NO (r = 0.57, p < 0.05) and Δe°T (r = 0.525, p < 0.05). In asthma patients, Q_aw was reduced 30 minutes after the inhalation of budesonide 400 μg (21.0 ± 2.3 μl/ml/min, p < 0.05) but was not affected by salbutamol.Δe°T correlates with Q_aw and exhaled NO in asthmatic patients and therefore may reflect airway inflammation, as confirmed by the rapid response to steroids.     

支气管扩张合并支气管哮喘患者的病原菌检测及危险因素分析

目的分析支气管扩张合并支气管哮喘患者的病原菌及危险因素。方法选取湖州市中心医院115例支气管扩张合并支气管哮喘患者作为观察组,另选取同期110例健康体检者作为对照组。分析患者病原菌的组成、耐药性及发病危险因素。结果观察组患者送检痰样本经痰培养,阳性检出者68例,阳性率为59.13%(68/115)。全部样本共分离出104株病原菌,其中革兰阴性菌92株(以铜绿假单胞菌最多,占54.81%),革兰阳性菌8株,真菌4株。药敏试验结果表明革兰阴性菌对复方新诺明、头孢曲松、左旋左氧氟沙星和阿莫西林/克拉维酸等药物的耐药性均较高,对妥布霉素、亚胺培南、头孢哌酮/舒巴坦和哌拉西林的耐药性较低。Logistic回归分析显示,吸烟史、药物过敏史、食物过敏史、过敏性鼻炎、哮喘、过敏性肺炎、慢性支气管炎及慢性阻塞性肺疾病均是支气管扩张伴支气管哮喘发生的危险因素。结论支气管扩张合并支气管哮喘患者其病原菌以革兰阴性菌为主,吸烟史、药物过敏史、食物过敏史、过敏性鼻炎等是支气管扩张伴支气管哮喘发生的危险因素。     

染料木黄酮对哮喘豚鼠肺部炎症和气道重塑的预防作用

目的：研究蛋白酪氨酸激酶（PTK）抑制剂染料木黄酮对哮喘豚鼠肺部炎症和气道重塑的作用。方法：成年雄性豚鼠30只,随机分成3组（n=10）：对照组（C组）、哮喘组（A组）和染料木黄酮干预组（B组）,以腹腔内注射联合雾化吸入卵蛋白复制哮喘模型。测支气管肺泡灌洗液（BALF）中细胞总数及其分类数,测细支气管炎症细胞浸润及支气管重塑指标,免疫纽化方法测磷酸化酪氨（p-tyrosine）在肺组织中的表达。结果：A组BALF中细胞总数、嗜酸性粒细胞分类与C组比较明显增加,B组与A组比较明显降低,差异有统计学意义（P〈0．01）;A组细支气管嗜酸性粒细胞（E）数和淋巴细胞（L）数较C组明显增多,B组与A组比较明显降低,差异有统计学意义（P〈0．01）;B组细支气管重塑较A组明显减轻（P〈0．01）,与C组比较,差异无统计学意义（P〈0．05）;免疫组化显示p-tyrosine在支气管平滑肌、支气管上皮、血管滑平滑肌及炎性细胞均有表达,尤其以支气管和血管平滑肌及炎性细胞明显,A组比C组表达明显增高,差异有统计学意义（P〈0．01）,而B组与C组比较,无明显差别（P〉0．05）。结论：PTK对哮喘豚鼠肺部炎症和支气管重塑具有促进作用：PTK抑制剂染料木黄酮对哮喘豚鼠肺炎症和支气管重塑具有预防和抑制作用。     

Enhanced CCL26 production by IL-4 through IFN-gamma-induced upregulation of type 1 IL-4 receptor in keratinocytes

A Th2 cytokine, IL-4, induces various chemokines from epidermal keratinocytes which play crucial roles in the pathogenesis of skin disorders such as atopic dermatitis. In contrast, the role of IFN-γ, a Th1 cytokine, on eosinophilic skin inflammation is unclear. This study investigated the effects of IFN-γ on IL-4-induced production of eotaxin-3/CCL26, a potent chemoattractant to eosinophils, in normal human epidermal keratinocytes (NHEK). When the cells were stimulated with IL-4 and IFN-γ simultaneously, IL-4-induced CCL26 production was attenuated. In contrast, prior stimulation with IFN-γ enhanced IL-4-induced CCL26 production. NHEK constitutively expressed type 1 IL-4 receptor, and expression at the cell surface was upregulated by stimulation with IFN-γ. This upregulation resulted in an enhanced IL-4-mediated cellular signal. These results indicate that IFN-γ has opposite effects on IL-4-induced CCL26 production in NHEK depending on the time of exposure. Thus, changes in IL-4R expression by IFN-γ might modulate eosinophilic skin inflammation.     

Serum concentrations of androstenediol and androstenediol sulfate, and their relation to cytokine production during and after normal pregnancy

Since it is known that androstenediol (ADIOL) has potent immunoregulatory effects, changes in ADIOL levels during and after pregnancy might affect the maternal immune system. We examined serum concentrations of ADIOL and androstenediol 3-sulfate (ADIOLS) together with IFN-gamma and IL-4 production levels during pregnancy and after delivery up to 10-11 months postpartum. The subjects were 73 normal pregnant, 76 normal postpartum, and 28 normal non-pregnant women. ADIOL and ADIOLS were measured using EIA and GC/MS, respectively. The cytokine levels in the supernatant of whole-blood cultures stimulated with phorbol 12-myristate 13-acetate and ionomycin were measured using ELISA. ADIOL levels significantly decreased compared to non-pregnant levels in the first trimester (P < 0.05) and were reversed in the third trimester (P < 0.05). After pregnancy, ADIOL levels gradually declined, and a significant decrease was observed at 10-11 months postpartum (P < 0.05). ADIOLS levels were significantly lower in the third trimester (P < 0.05) and significantly higher at the first month postpartum (P < 0.001) compared to non-pregnant women. IFN-gamma and IL-4 levels decreased during pregnancy and subsequently increased postpartum. On the other hand, we found significant negative correlations between ADIOL concentrations and production levels of IFN-gamma (P < 0.05) or IL-4 (P < 0.05). These findings suggest that ADIOL may be involved in modifying the maternal immune response during and after pregnancy.     

The effect of house design and environment on fungal movement in homes of bronchial asthma patients

The effect of house building design and environment on the fungal movement in the houses of 41 bronchial asthma (BA) patients has been investigated by examining house dust. The presence and composition of fungi were determined and compared in relation to building structure, house age, size of living room, main flooring material, presence of a living-room rug or air purifier, and frequency of vacuum cleaning. Among these elements, fungal CFU apparently varied only between building structure: wooden-board houses had significantly higher numbers of fungi than reinforced concrete houses (p < 0.01), and wooden mortar or iron-framed prefabricated houses had significantly higher numbers of fungi than reinforced concrete houses (p < 0.05). Classification of the types of fungi present in the house dust of BA patients showed that, regardless of the building designs, there were high levels of osmophilic fungi (group A) and fungi that survive at relatively dry conditions (group B), whereas fungi that survive in very wet conditions (group D) were present at low frequency. This revised version was published online in August 2006 with corrections to the Cover Date.     

支气管哮喘与呼吸道微生态关系的研究进展

人体是个巨大的生态系统,各个器官的表面附着大量的微生物,微生物群通过与宿主细胞之间的相互作用来保证机体的正常营养代谢和微生态稳定。长期以来由于呼吸道的生理功能和特性,其微生物菌群的调节作用没有引起足够重视。自“肠-肺轴”的提出,更多学者开始致力于研究呼吸道微生态,并发现一些呼吸道疾病如慢性阻塞性肺疾病、特发性肺纤维化以及支气管哮喘等的发生发展与呼吸道微生态存在一定的关系,这为进一步研究呼吸道疾病,并寻求更好的治疗方式提供新的方向和选择。本文就支气管哮喘与呼吸道微生态之间的作用关系作一综述。     

银杏叶提取物对豚鼠哮喘模型血红素氧合酶-1表达的影响

目的探讨银杏叶提取物(Egb761)对豚鼠哮喘模型血红素氧合酶-1(HO-1)表达的影响.方法 将30只豚鼠随机分为3组(n=10)(1)正常组;(2)哮喘组;(3)治疗组.测定全血一氧化碳血红蛋白(COHb)的百分比含量、气道阻力并观察气道壁嗜酸性粒细胞(EOS)浸润情况, 用免疫组织化学染色方法观察HO-1在豚鼠肺组织中的表达变化.结果各组气道上皮细胞HO-1阳性表达的平均吸光度分别为 0.170±0.020、0.707±0.058、0.397±0.034.哮喘组HO-1的表达水平显著高于正常组(P<0.01).治疗组HO-1的表达水平显著低于哮喘组(P<0.01). 结论银杏叶提取物能显著抑制哮喘豚鼠气道壁内上皮细胞HO-1的表达,提示银杏叶提取物抑制HO-1的表达可能是银杏叶提取物治疗哮喘的作用机制之一.     

Occurrence of Astringent Oligomeric Proanthocyanidins in Legume Seeds

The distribution of oligomeric proanthocyanidins in legume seeds was investigated in connection with organoleptic astringency. The seeds contained various kinds of oligomers (dimers?hexamers). The total oligomer contents were at least 0.040% in azuki beans, 0.017% in black soybeans, 0.005% in mung beans and a trace amount in regular soybeans. Each aliquot of aqueous solution of partially purified proanthocyanidin oligomers tasted astringent even at a concentration of 0.001% (w/v). The possible contribution of oligomeric proanthocyanidins and polymeric proanthocyanidins to the astringent off-taste of legume seeds is discussed.     

Effect of T helper 1 (Th1)/Th2 cytokine on chemokine-induced dendritic cell functions

Effects of T helper 2 (Th2) and Th1 cytokines, interleukin (IL)-4, and interferon (IFN)-gamma, respectively, on chemokine-induced DC migration and endocytosis are not well understood. We investigated herein the effects of these cytokines on chemokine-induced functions of murine myeloid DCs. As expected, immature DCs markedly migrated to CCL3 but not CCL19, while mature DCs showed vigorous migration in response to CCL19 but not CCL3. Both IL-4 and IFN-gamma significantly decreased CCL3-induced migration of immature DCs. In contrast, these cytokines exerted no significant effects on CCL19-induced migration of mature DCs. Of note, both IL-4 and IFN-gamma markedly enhanced CCL3-induced endocytosis of immature DCs. The messenger RNA level of CCR5, a CCL3 receptor, in immature DCs was slightly increased by IL-4 or IFN-gamma treatment. These results demonstrate that these Th1/Th2 cytokines can act to either inhibit or enhance chemokine-mediated DC functions, and may play a role in increasing antigen uptake by immature DCs at inflammatory sites.