支气管扩张症发病的免疫机制研究进展

支气管扩张症是一种常见的慢性支气管疾病。其发病基础为支气管壁的炎性损伤和支气管阻塞的相互作用。病因涉及诸多方面，其中免疫学方面的有关发病机制受到了各国学者的关注。本文就体液免疫、细胞免疫、其它致病因素及治疗方面阐述了支气管扩张症发病机制中可能存在的免疫学因素。     

支气管扩张症发病机制及治疗进展

支气管扩张症在世界范围内发病率均有所增加,但其异质性较强,目前对其病因、发病机制及有效治疗等方面的研究相对较少,我们对这一疾病还有待进一步认识.目前认为其发病机制主要有免疫失调及细菌定植两个方面.近来大环内酯类抗生素对支气管扩张症的治疗方面也取得了一些进展.本文就非囊性纤维化支气管扩张症流行病学、病因学、发病机制及治疗方面的进展进行综述.     

支气管灌洗术在支气管扩张症治疗中的作用

目的 分析支气管灌洗术在支气管扩张症治疗中的效果.方法 选取82例支气管扩张症者予以支气管灌洗术作为观察组,再抽取予以抗生素等常规治疗的80例支气管扩张症者对比作为对照组;观察、分析两组临床疗效等.结果 观察组近期疗效（总有效率86.59%）、远期效果（82.93%）,均高于对照组;且观察组临床症状、体征消失或改善时间和抗生素应用时间和住院时间较对照组缩短（P〈0.05）.结论 支气管灌洗术在支气管扩张症治疗中应用效果显著且起效迅速.     

中性粒细胞弹性蛋白酶在支气管扩张症发病中的作用及治疗对策

中性粒细胞释放的中性粒细咆弹性蛋白酶(NE)通过多种途径促进支气管扩张症的发生发展,在支气管扩张症发病中起着重要的作用。为对抗其活性,可应用抗生素、提纯或重组的蛋白酶抑制物、合成NE抑制剂、抗氧化剂及天然抑制物等措施。     

蛋白激酶C信息通道在支气管哮喘炎症细胞中的作用

支气管哮喘有多种炎症细胞参与其发病过程，蛋白激酶Ｃ与其中的淋巴细胞，肥大细胞，嗜碱粒细胞，嗜酸粒细胞，核／巨噬细胞及外周血单个核细胞等的功能调控密切相关。     

细胞因子和炎症介质在急性呼吸窘迫综合征发病机制中的作用

急性呼吸窘迫综合征（acute respiratory distress syndrome,ARDS）是由多种原发性疾病过程中发生的急性进行性缺氧性呼吸衰竭（respiratory failure） ,是急性肺损伤（acute lung injury,ALI）的严重阶段,其特征性的病理生理表现为肺实质炎症反应而导致的弥漫性肺泡上皮和肺微血管内皮的严重损伤.在美国每年估计约有190 000 ～200 000例ALI/ARDS成年患者,以及还有大量的ALI/ARDS儿童患者.     

非囊性纤维化性支气管扩张症的免疫调节机制

支气管扩张症是慢性炎症性支气管疾病的一种,病理上表现为一个或多个支气管的永久性扩张。非囊性纤维化性支气管扩张症的发病往往与反复感染、免疫缺陷或自身免疫性疾病相关,也有相当一部分呈特发性。细菌定植、气道炎症和气道结构损伤这样一个恶性循环导致了支气管扩张症的发生,其中气道炎症承前启后,是整个恶性循环的关键,因此研究气道炎症的免疫调节机制对理解其发病机理具有重要意义,并可指导支气管扩张症的药物研发。本文着重讨论了与支气管扩张症的发病密切相关的细胞与分子免疫调节机理,并阐述了细菌慢性定植的机理,还结合免疫调节讨论了支气管扩张症的新药研发。     

白介素—17在支气管哮喘气道炎症发病机制中的作用

支气管哮喘的加重与气道内中性粒细胞的大量浸润有密切关系，晚近研究表明，淋巴细胞相关因子白介素－17（IL－17）在T细胞的激活及中性粒细胞在气道募集方面具有重要作用。应进行临床研究以评价IL－17的作用机制，以为今后的药物治疗奠定基础。     

支气管扩张症急性加重期研究进展

<正>支气管扩张症(支扩)是各种原因引起的支气管树的病理性永久性扩张,导致反复发生化脓性感染的气道慢性炎症。临床表现为持续或反复性咳嗽咳痰,有时伴有咯血,可导致呼吸功能障碍及慢性肺源性心脏病。支气管扩张症病程长,病变不可逆转,由于反复感染,特别是广泛性支气管扩张可严重损害患者肺组织和功能,严重影响患者的生活质     

胸腔镜手术治疗支气管扩张症

目的探讨胸腔镜手术在支气管扩张症中的应用价值。方法2002年7月～2010年3月,对20例支气管扩张症行胸腔镜手术治疗。12例施行胸腔镜辅助小切口肺叶切除术,8例施行胸腔镜肺楔形切除术。结果1例因出血中转开胸。全组无围手术期死亡,围手术期并发症3例：术后肺持续漏气2例,肺部感染1例。平均胸管置管时间3．6d（2～7d）,术后住院平均9d（7～14d）。20例随访3～36个月,均恢复良好。结论胸腔镜手术治疗支气管扩张症在技术上是安全可行的,对于具有手术指征需行肺楔形切除或肺叶切除的支气管扩张症患者,胸腔镜手术是一种值得推荐的手术方式。     

Relation between inflammatory cytokine levels in serum and bronchoalveolar lavage fluid and gene polymorphism in young adult patients with bronchiectasis

Aim

Bronchiectasis develops as a result of genetic and environmental factors and its etiopathogenesis is not still clear. Recent studies have revealed that inflammatory cytokines, which are formed as a result of chronic infection and inflammation, play a role in the pathogenesis of bronchiectasis. For this purpose, the level of inflammatory cytokines in bronchiectasis and the presence or absence of a genetic predisposition with the gene polymorphism of these cytokines was investigated.

Material and methods

A total of 60 patients, 40 study cases and 20 controls, which were monitored with the diagnosis of bronchiectasis were included in the study. In these individuals, cytokine levels [interleukin (IL)-6, IL-8, IL-10, and tumor necrosis factor (TNF)-α] in serum and bronchoalveolar lavage (BAL) fluid, along with the routine blood tests, were determined. Furthermore, the polymorphism in IL-6, IL-8, IL-10, and TNF-α cytokine genes and its frequency were studied in the obtained DNA by the automatic sequence analysis method and the results were compared.

Findings

It was found that in serum and BAL fluid of the patient group, the IL-8 level was high, whereas the IL-10 level was low (P<0.05). No significant difference was detected in the other cytokines (P>0.05). It was found that in cytokine gene polymorphisms IL-8 -251 A/T, IL-10 -592 A/C, and IL-10 -819 T/C genotypes are associated with increased risk of bronchiectasis. It was detected that the IL-8 -251 A/T genotype increased the risk of having the disease by 4.19 fold. (OR =4.19, 95% CI =1.24-14.17, P=0.021). The IL-10 -592 C/A genotype increased the risk of having the disease by 5.71 fold (OR = 5.71, 95% CI =1.35-24.06, P=0.017) and the IL-10 -819 T/C genotype increased the risk of having the disease by 5.06 fold (OR =5.06, 95% CI =1.20-21.27, P=0.048). No significant correlation was found between the other polymorphisms and bronchiectasis.

Conclusions

The IL-8, IL-10 levels and the gene polymorphism of these cytokines differ. In addition to detecting higher levels of pro-inflammatory IL-8 and lower levels of anti-inflammatory IL-10, detection of gene polymorphism related to these two cytokines in bronchiectasis gives rise to the thought that cytokines may have role in a predisposition to bronchiectasis. However, as the number of patients is small, precise remarks could not be made on this subject. There is need for further studies include a larger number of patients.     

Role of regulatory T cell in the pathogenesis of inflammatory bowel disease

Regulatory T(Treg) cells play key roles in various immune responses. For example, Treg cells contribute to the complex pathogenesis of inflammatory bowel disease(IBD), which includes Crohn’s disease and ulcerative colitis during onset or development of that disease. Many animal models of IBD have been used to investigate factors such as pathogenic cytokines, pathogenic bacteria, and T-cell functions, including those of Treg cells. In addition, analyses of patients with IBD facilitate our understanding of the precise mechanism of IBD. This review article focuses on the role of Treg cells and outlines the pathogenesis and therapeutic strategies of IBD based on previous reports.     

Persistent sputum cellularity and neutrophils may predict bronchiectasis

BACKGROUND:

Quantitative cell counts in sputum provide an accurate assessment of the type and severity of bronchitis.

OBJECTIVE:

To examine whether sputum cell counts could identify bronchiectasis in patients with recurrent bronchitis.

METHODS:

A retrospective survey of a clinical database (January 2004 to January 2005) of quantitative cell counts from sputum selected from expectorate in patients with obstructive airways diseases was used to identify predictors of bronchiectasis using ROC curves. This was prospectively evaluated (February 2005 to April 2008) using high-resolution computed tomography scans of thorax that were independently scored by a radiologist who was blinded to the clinical details.

RESULTS:

The retrospective survey identified 41 patients with bronchiectasis among 490 patients with airway diseases. Total cell count of 60×10⁶/g or greater of the selected sputum with predominant neutrophils on two occasions had a sensitivity of 86.7%, a specificity of 87.5%, and positive and negative predictive values of 93% and 78%, respectively, to identify bronchiectasis. In the prospective study, 10 of 14 (71%) patients who met these criteria were identified to have bronchiectasis. Both total cell count and the percentage of neutrophils correlated with radiographic bronchiectasis severity.

CONCLUSIONS:

Persistent or recurrent intense sputum cellularity with neutrophilia is suggestive of bronchiectasis.     

Th17细胞在炎症性肠病发病机制作用的研究进展

炎症性肠病的病因和发病机制尚未完全明确。最近的研究表明,Th17细胞及与其相关的细胞因子、Th细胞亚群所导致的炎症过程在炎症性肠病的发生发展中起重要作用。本文就Th17的分化调控机制及Th17与其相关的细胞因子、Th细胞亚群在炎症性肠病的发病机制中的作用作一概述。     

Suppression of inflammatory cytokine secretion by granulocyte/monocyte adsorptive apheresis in active ulcerative colitis

To elucidate the molecular mechanisms involved in the therapeutic effects of granulocyte/monocyte adsorption apheresis, changes were investigated in the cytokine responses of peripheral blood mononuclear cells (PBMC) before and after granulocyte/monocyte adsorptive apheresis in ulcerative colitis (UC) patients. Four patients with active UC were enrolled. All patients responded to granulocyte/monocyte adsorptive apheresis. A total of 20 sessions of four patients were analyzed. Peripheral blood mononuclear cells were isolated from peripheral venous blood within 5 min before and after each session of granulocyte/monocyte adsorptive apheresis. The cells were stimulated with interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha for 24 h, and the secreted IL-8 and IL-6 levels were determined by enzyme-linked immunosorbent assay (ELISA). IL-1beta-induced IL-8 and IL-6 secretion was significantly decreased after granulocyte/monocyte adsorptive apheresis. TNF-alpha-induced IL-8 secretion was also significantly decreased after apheresis, but there was no significant difference in TNF-alpha-induced IL-6 secretion (P = 0.052). In conclusion, granulocyte/monocyte adsorptive apheresis down-regulates the IL-1beta- and TNF-alpha-induced inflammatory responses in PBMC. The induction of hyporesponsiveness to pro-inflammatory cytokines may be an important factor mediating the clinical effects of granulocyte/macrophage adsorptive apheresis in UC patients.     

双歧杆菌对实验性结肠炎中趋化因子的影响

目的观察双歧杆菌在三硝基苯磺酸（TNBS）／乙醇诱导的实验性结肠炎的作用,并探讨其作用机制。方法40只SPF级SI）大鼠随机均分为正常组（N组）、模型组（M组）、双歧杆菌干预组（双歧杆菌预防性应用组：A组;双歧杆菌治疗组：B组）。TNBS／乙醇制备大鼠结肠炎模型。A组造模前7d始予双歧杆菌0．1mL,B组造模后予双歧杆菌0．1mL,双歧杆菌悬液浓度：1x10。cfu／mL,正常组与模型组生理盐水2mL,连续灌胃14d。观察各组大鼠结肠炎疾病活动指数（DAI）,评价结肠大体形态损伤指数（CMDI）和组织学损伤指数（TDI）,免疫组织化学法检测结肠组织CCL20、CCR6的表达,EL／SA法检测血清中CCL20、CCR6、TNF-α和IL-10含量。结果双歧杆菌干预组DAI、CMDI和TDI评分明显低于模型组,血清TNF—d、CCL20、CCR6及结肠组织CCL20、CCR6的表达明显降低（P均〈0．01）,而血清IL-10水平升高（P〈0．01）。A组与B组差异无统计学意义。结论双歧杆菌可能通过降低组织及血清CCL20及其受体CCR6表达,调节促炎因子与抗炎因子的平衡,对实验性结肠炎发挥治疗作用,且提前应用能提高疗效,发挥更好的作用。     

Animal models of intestinal inflammation: new insights into the molecular pathogenesis and immunotherapy of inflammatory bowel disease

Inflammatory bowel diseases (IBDs) in humans are complex chronic inflammatory disorders of largely unknown cause. Several mouse models that in some respects resemble human IBDs have recently been developed and have provided new insights into immunoregulatory processes in the gut. Both genetic and environmental factors have been shown to be involved in chronic intestinal inflammation. In most of the models CD4⁺ T lymphocytes have been identified as central mediators of inflammation. Inappropriate activation of T_H1-dominated cytokine pathways upon contact with luminal bacterial antigens and lack of tolerance appear to be crucial for intestinal pathology. We present a brief overview of important animal models of IBD and describe the recent progress in understanding the mechanisms that contribute to chronic intestinal inflammation. Furthermore, novel immunotherapeutic approaches derived from such animal models are discussed. Accepted: 18 April 2000