粒细胞巨噬细胞集落刺激因子和白细胞介素5在鼻息肉中表达

目的探讨粒细胞巨噬细胞集落刺激因子(granuIocyte-macrophage colony-stimulating factor,GM-CSF)和白细胞介素5(interleukin-5,IL-5)在单发鼻息肉组织及多发鼻息肉组织中的表达水平的差异。方法分别采用ELISA法及免疫组化SP法检测单发鼻息肉组30例、多发复发鼻息肉组23例及对照组15例(下鼻甲部分切除术患者下鼻甲黏膜标本)中GM- CSF及IL-5的表达状况。结果多发性鼻息肉组中GM- CSF及IL-5表达量均明显高于单发鼻息肉组,单发鼻息肉组明显高于对照组,两组间差异均有统计学意义(P<0.01)。结论鼻息肉的多发、复发机制可能与GM- CSF及IL-5的高表达水平有关,它们在鼻息肉的发病机制中占有重要地位。     

白细胞介素-6和8在鼻息肉组织中的表达

目的探讨白细胞介素（interleukin,IL）-6、8与鼻息肉（nasalpolyps,NP）发病机理的关系，进一步探讨炎症及变态反应对鼻息肉发生及发展的影响。方法采用放射免疫分析法研究细胞因子(cytokines)成员中IL-6，IL-8在鼻息肉组织匀浆、鼻息肉患者血清、正常成人血清及脐血中的表达及其意义。结果鼻息肉组织匀浆中IL-6平均质量浓度为（2.7658±0.3797）ng/L，IL-8平均质量浓度为（4.1877±0.1758）ng/L，与鼻息肉患者血清、正常血清及脐血相比，鼻息肉组织中IL-6、IL-8过度表达，差异有显著性（P<0.01），但患者血清、正常血清及脐血之间IL-6、IL-8表达无明显差异。IL-6、IL-8表达与鼻息肉患者的性别无关，变应原试验阳性组及阴性组之间亦无明显差异。结论IL-6及IL-8在鼻息肉组织中过度表达，其通过局部微环境调控，在鼻息肉的发生发展过程中起重要作用，而变态反应并非鼻息肉发生的必备条件和启动因素。     

白介素-5在变应性鼻炎鼻黏膜中的表达及意义

目的：了解白介素 5（IL 5）在变应性鼻炎鼻粘膜内浸润的炎性细胞中的表达及分布,探讨IL 5与嗜酸性粒细胞积聚及发病机制的关系。方法：采用免疫组化染色法（SP法）对变应性鼻炎下鼻甲粘膜（A组）、单发鼻息肉组织（B组）、无变应性鼻炎下鼻甲粘膜组织（C组）切片进行IL 5染色,对IL 5染色阳性细胞计数分类,对统计结果行方差分析。结果：A、B两组组织中可见较多的IL 5阳性染色细胞,多见嗜酸性细胞、淋巴细胞、中性粒细胞等阳性染色,两组IL 5阳性细胞总数、Eos计数无统计学差异,但均高于C组（P＜0.01）。结论：IL 5在变应性鼻炎鼻粘膜、鼻息肉组织内浸润的多种炎性细胞中表达,能客观反映免疫或炎症反应的程度,可作为变应性鼻炎诊断评分系统的补充。     

平阳霉素对鼻息肉病组织中肿瘤坏死因子表达的影响

目的通过观察平阳霉素对鼻息肉病组织中肿瘤坏死因子(tumornecrosisfactor,TNF)表达的影响,探讨平阳霉素治疗鼻息肉病的机制。方法应用TNF单克隆抗体分别对19例鼻息肉病患者平阳霉素治疗前和治疗后鼻息肉病组织标本进行免疫组化染色,观察TNF在鼻息肉病组织中的表达和分布。结果平阳霉素治疗后鼻息肉病组织中的腺体数和血管数比治疗前明显减少,差异有显著性意义(P<0.05);平阳霉素治疗后鼻息肉病鼻息肉组织中腺体和血管TNF阳性表达率明显降低(P<0.05);上皮细胞TNF阳性表达率治疗前为(45.37±12.16)%,治疗后为(28.49±11.93)%,差异有显著性意义(P<0.05)。结论平阳霉素可减少鼻息肉病组织中腺体和血管数量以及减少上皮细胞、腺体和血管中TNF表达。     

IL-17在鼻息肉中的表达及其意义

目的：研究伴变应性体质和不伴变应性体质的鼻息肉患者息肉中IL-17的表达及与病理特征的关系。方法：30例鼻息肉患者根据皮肤点刺实验分为伴变应性体质组和不伴变应性体质组,通过苏木精一伊红染色法嗜酸粒细胞浸润程度评价组织学特征,运用ELISA及RT—PCR方法检测IL-17在鼻息肉中的表达。结果：伴变应性体质组嗜酸粒细胞浸润明显高于不伴变应性体质组（P〈O．01）;两组息肉组织中IL-17蛋白及mRNA水平均显著高于对照组（P〈O．01或P〈0．05）,且变应性体质组IL-17水平明显高于不伴变应性体质组,鼻息肉患者IL-17水平与嗜酸粒细胞浸润呈正相关。结论：IL-17在鼻息肉组织中表达明显上调,且在伴变应性体质组中水平更高,提示IL-17可能在鼻息肉的发病机制中发挥重要作用,变应性因素在鼻息肉形成中可能是通过促进IL-17曲立牛而,卉＇枷曲     

鼻息肉组织中T-细胞亚群的分布及2种白细胞介素表达的初步研究

目的　探讨T 淋巴细胞及细胞因子白细胞介素 (interleukin ,IL)调节功能的紊乱在鼻息肉发病中的重要作用。方法　应用免疫组织化学的方法检测 32例鼻息肉标本和 6例下鼻甲粘膜对照标本中T 细胞亚群 (CD4 和CD8 细胞 )以及细胞因子IL 5、IL 10阳性细胞的表达情况。并进行统计学分析。结果　鼻息肉组织中可见各种炎细胞浸润 ,CD4 和CD8 细胞数增多 (P <0 0 0 1) ;其中CD4 细胞明显多于CD8 细胞 (P <0 0 0 1)。鼻息肉组织IL 5和IL 10阳性细胞明显增多 ,(P <0 0 0 1) ,且IL 5 细胞多于IL 10 细胞 (P <0 0 5 )。IL 5 细胞以浆细胞和淋巴细胞为主。在鼻息肉血管和腺体周围 ,CD4 CD8 细胞数比值与IL 5 IL 10 细胞数比值呈显著正相关 (r=0 78,P <0 0 1)。结论　鼻息肉的形成与CD4 T 淋巴细胞和细胞因子IL 5的高表达有关。以浆细胞和淋巴细胞浸润为主的鼻息肉应作为鼻息肉病理学特征的一个必要补充。细胞免疫和体液免疫紊乱以及细胞因子分布失衡在鼻息肉免疫病理中发挥着至关重要的作用。     

鼻息肉组织中T—细胞亚群的分布及2种白细胞介素表达？…

目的 探讨Ｔ－淋巴细胞及细胞因子白细胞介素（ｉｎｔｅｒｌｅｕｋｉｎ,ＩＬ）调节２功能的紊乱在鼻息肉发病中的重要作用。方法 应用免疫组织化学的方法检测３２例鼻息肉标本和６例下鼻甲粘膜对照标本中Ｔ－细胞亚群（ＣＤ＾＋４和ＣＤ＾＋８细胞）以及细胞因子ＩＬ－５、ＩＬ－１０阳性细胞的表达情况。并进行统计学分析。结果 鼻息肉组织中可见各种炎细胞浸润,ＣＤ＾＋４和ＣＤ＾＋８细胞数增多（Ｐ〈０．００１）;其中ＣＤ     

Expression of MUC5AC mRNA in the goblet cells of human nasal mucosa

OBJECTIVES/HYPOTHESIS: Mucus hypersecretion is a common feature in chronic sinusitis with polyps. Because mucus hypersecretion is commonly accompanied by goblet cell hyperplasia, it is important to identify which mucin gene mRNAs are expressed in the goblet cells of the surface epithelium in the human airway. This study aims to investigate the pattern of expression of MUC5AC messenger RNA (mRNA) in the goblet cells of human nasal mucosa. METHODS: Six nasal polyps, five inferior turbinate mucosa specimens, and three normal-appearing mucosa specimens of the posterior ethmoid sinus were obtained. Each of the specimens was cut into 10-microm-thick serial frozen sections, and in situ hybridization of MUC5AC mRNA was performed with an oligonucleotide probe. Alcian blue (pH 2.5)-periodic acid-Schiff (AB-PAS) staining was performed on the serial sections. RESULTS: In human nasal polyps, MUC5AC mRNA was expressed in the cytoplasm of most of the goblet cells. However, in the inferior turbinate, MUC5AC mRNA was expressed in only some of the goblet cells. On the contrary, in the normal-appearing mucosa of the posterior ethmoid sinus, MUC5AC mRNA was barely expressed in the goblet cells. Furthermore, MUC5AC mRNA was mainly expressed in some of the PAS-positive goblet cells. CONCLUSIONS: Only a portion of the goblet cells in the human nasal mucosa expressed MUC5AC mRNA. This result suggests that surface goblet cells might have other mucin genes, in addition to MUC2 and MUC5AC.     

Eotaxin和Eotaxin-2在鼻息肉病和鼻息肉组织中的表达及意义

目的：了解嗜酸粒细胞（EOs）趋化因子Eotaxin、Eotaxin-2在人鼻息肉病和鼻息肉组织中的表达情况,探讨鼻息肉与鼻息肉病发病机制上的异同。方法：采用免疫组织化学方法（SP法）检测15例鼻息肉病患者（鼻息肉病组）、13例鼻息肉患者（鼻息肉组）的息肉组织和8例行鼻中隔偏曲矫正术患者的中鼻甲组织（对照组）中Eotaxin和Eotaxin-2的表达。结果：Eotaxin-2在对照组、鼻息肉组和鼻息肉病组3组间呈递增表达,且每2组间比较均差异有统计学意义（均P〈0．05）;Eotaxin在鼻息肉病和鼻息肉组中的表达均显著高于对照组（均P〈0．05）,而在鼻息肉病组与鼻息肉组间表达差异无统计学意义。结论：Eotaxin和Eotaxin-2可能均参与了鼻息肉病与鼻息肉的炎症反应过程,Eotaxin-2在鼻息肉病和鼻息肉组织之间的不同表达提示它可能是鼻息肉病与鼻息肉发病机制不同的重要原因之一。     

The pathogenesis of nasal polyposis by immunoglobulin E and interleukin-5 is completed by transforming growth factor-beta1

OBJECTIVES/HYPOTHESIS: Nasal polyps are benign mucosal protrusions into the nasal cavity of multifactorial origin and are characterized by chronic mucosal inflammation. The suggested multifactorial pathological mechanisms comprise several factors including cytokines and immunoglobulin E (IgE). The study was designed to examine the suggested roles of IgE, interleukin-5 (IL-5), and transforming growth factor-beta1 (TGF-beta1) in the pathogenesis of nasal polyposis. METHODS: Nasal polyps (n = 34) and healthy nasal mucosa samples (n = 9) were taken during routine endonasal surgeries. Immunoglobulin E (n = 13), IL-5 (n = 22), and TGF-beta1 (n = 27) concentrations were measured with enzyme-linked immunosorbent assay technique in homogenized polyp tissue and in control mucosa. Atopic and nonatopic groups were selected and compared. Histomorphological examination and immunohistochemical analysis to detect IL-5 and TGF-beta1 were performed in five specimens. RESULTS: The level of tissue-bound IgE was significantly higher in polyps compared with control specimens and in atopic compared with nonatopic polyps, but between nonatopic polyps and control specimens the difference was not significant. However, significant correlation was found between tissue and serum IgE in the complete polyp (P =.001) and atopic polyps group (P =.05). Tissue IL-5 concentration was significantly higher in polyps compared with control specimens, in which it was below the limit (15 pg/mL), and there was no difference between atopic and nonatopic polyps. In atopic polyps there was significant correlation between tissue IgE and IL-5. Transforming growth factor-beta1 concentration proved to be significantly higher in control mucosa than in polyps, with no difference between atopic and nonatopic polyps. Immunohistochemical analysis revealed numerous IL-5-positive eosinophil cells and TGF-beta1 positivity in the lamina propria of polyp samples, but none in control specimens. CONCLUSIONS: High tissue TGF-beta1 quantity in healthy nasal mucosa without its active form on the cell surface and its low quantity in polyps may reflect its essential role in the inhibitory mechanisms of nasal polyposis. Interleukin-5 plays a key role in the eosinophil recruitment and activation, and both atopic and nonatopic pathways might activate this process. The main sources of IL-5 and TGF-beta1 are the eosinophils and macrophages. Immediate hypersensitivity, besides other mechanisms, might be related to atopic polyps, but the involvement of other, local allergic mechanisms in IgE production of nonatopic polyp tissue cannot be excluded.     

Nasal interleukin-5, immunoglobulin E, eosinophilic cationic protein, and soluble intercellular adhesion molecule-1 in chronic sinusitis, allergic rhinitis, and nasal polyposis

OBJECTIVE: To compare concentrations of interleukin-5 (IL-5), immunoglobulin E (IgE), eosinophilic cationic protein (ECP), and soluble intercellular adhesion molecule-1 (sICAM-1) in nasal secretion and serum of patients with chronic nonallergic sinusitis, allergic rhinitis, and nonallergic nasal polyposis to obtain information about the pathogenesis of these diseases. METHODS: Nasal secretion and serum were analyzed by routine enzyme-linked immunosorbent assay techniques. Nineteen patients with chronic nonallergic sinusitis, 24 patients with seasonal allergic rhinitis, and 18 patients with nonallergic nasal polyposis were included in the study. Eight healthy, nonallergic probands served as control subjects. RESULTS: Significantly elevated concentrations of IL-5 (5-fold, P < .05) and IgE (15-fold, P < .01) were detected in nasal secretion of patients with allergic rhinitis (IL-5, 51.8 +/- 13.2 pg/mL; IgE, 41.9 +/- 20.9 kU/L) or nonallergic nasal polyposis (IL-5, 57.9 +/- 36.9 pg(mL; IgE, 40.5 +/- 20.2 kU/L) compared with controls (IL-5, 10.6 +/- 7.8 pg/mL; IgE, 2.8 +/- 0.5 kU/L) or with patients with chronic nonallergic sinusitis (IL-5, 16.5 +/- 13.2 pg/mL; IgE, 5.4 +/- 3.1 kU/L). There were no significant differences between patients with allergic rhinitis and those with nonallergic nasal polyposis. Concentrations of ECP were significantly elevated (sixfold, P < .01) in patients with allergic rhinitis (297.8 ng/mL +/- 173.1) compared with controls (52.4 +/- 28.0 ng/mL) or patients with chronic nonallergic sinusitis (44.8 +/- 40.1 ng/mL), whereas twofold higher concentrations (not significant) of ECP were observed in patients with nonallergic nasal polyposis (107.1 +/- 26.6 ng/mL). Significantly elevated concentrations of sICAM-1 in nasal secretion (threefold, P < .05) were detected only in patients with chronic nonallergic sinusitis (79.4 +/- 45.6 ng/mL). The elevated sICAM-1 nasal secretion values in this group correlated significantly (P < .05) to the serum values. CONCLUSIONS: Equally elevated concentrations of IL-5 and IgE in patients with allergic rhinitis and nonallergic nasal polyposis implicated similar pathogenic processes in both diseases. Whereas the pathogenesis of allergic rhinitis is IgE-specific, the pathogenesis of nasal polyps is not as clear. IL-5 was suggested to play a pivotal role in tissue eosinophilia, which was confirmed by data in the present study. Elevated concentrations of ECP were suggested to result from tissue eosinophilia--a characteristic of both diseases. Elevated concentrations of sICAM-1 in patients with chronic nonallergic sinusitis pointed to its key role in the recruitment of neutrophils into the inflamed tissue, whereas an important role in eosinophil recruitment was ruled out.     

鼻息肉中白介素-8的检测和意义

目的　探讨鼻息肉中白介素 8(interleukin 8,IL 8)的表达及作用。方法　应用免疫组化和酶联免疫吸附测定法 ,对 2 2例鼻息肉和 10例对照组 (鼻中隔偏曲者 )下鼻甲组织内IL 8的分布及含量进行测定。结果　IL 8免疫阳性染色物呈棕黄色颗粒 ,主要位于鼻息肉上皮细胞浆及炎性细胞浆 ,鼻息肉组织中IL 8的含量较对照组明显增高 ,鼻息肉组的吸收值范围在 32 2 0 6～ 2 0 91 41pg/ml之间 ,对照组的吸收值范围在 2 9 31～ 332 19pg/ml之间 ,2组之间差异有显著性 (P <0 0 0 1)。结论　IL 8可能是鼻息肉发病机理中诸多因素之一 ,深入了解这一作用对寻找鼻息肉有效的治疗方法可能有重要意义。     

Distribution of rantes and interleukin-5 in allergic nasal mucosa and nasal polyps.

Eosinophil-chemoattracting cytokines are thought to be important in the pathogenesis of allergic inflammation. However, little is known about the presence and significance of RANTES in nasal allergy and nasal polyps, two well-known rhinologic disorders characterized by eosinophil infiltration in the tissue. In order to evaluate the role of RANTES in eosinophil infiltration in vivo, the tissue distributions of RANTES and interleukin-5 (IL-5) and their correlation with eosinophil infiltration were investigated. Nasal mucosa specimens were obtained from 9 allergic and 12 control subjects, and nasal polyps from 6 allergic and 9 nonallergic subjects. All the subjects were divided into 4 groups: normal mucosa, allergic mucosa, nonallergic polyps, and allergic polyps. To identify the cellular localizations of RANTES and IL-5, we used specific immunohistochemical staining. We also investigated the differences in cytokine expression among the 4 groups, and the correlation between cytokine expression and eosinophil infiltration in the tissue. RANTES was expressed in the epithelium, endothelium, and some submucosal cells, while IL-5 was confined to the cells in the submucosa. Expression of both RANTES and IL-5 significantly increased in allergic mucosa and nasal polyps compared to normal mucosa; however, there was no significant difference in their expression between allergic and nonallergic polyps. Both cytokines had a significant correlation between their expression and either total or activated eosinophil numbers. The results of this study suggest that RANTES, as well as IL-5, plays a role in eosinophil recruitment in allergic nasal mucosa and nasal polyps in vivo.     

Significance and detection of interleukin-8 in human nasal polyps]

OBJECTIVE: To investigate the distribution and content of immunoreaction interleukin-8(IL-8) antigen in the human nasal polyps. METHODS: Twenty-two cases of nasal polyp and 10 cases of normal inferior turbinate were studied with immunohistochemical SABC method and ELISA method. RESULTS: Immunohistochemical results demonstrated that IL-8 antigen staining occurred predominantly within inflammatory and epithelium cell plasm. The level of IL-8 in nasal polyp tissue was higher than in normal control specimens. The value in nasal polyp tissue was in 322.06-2091.41 pg/ml, but in normal with a range of 29.31-332.19 pg/ml. The results demonstrated a remarkable difference between the two groups (P < 0.001). CONCLUSION: These data demonstrated the presence of IL-8 antigen in nasal polyps. Thus IL-8 likely plays a significant role in the pathogenesis of this disease process. There is an important significance of finding a potential treatment method.     

鼻息肉中IL-15mRNA的表达及其作用

目的 观察IL-15mRNA在鼻息肉与下鼻甲中表达的差异及其与Bcl-2、Bcl-XL表达的关系,明确鼻息肉中IL-15的来源,探讨其在鼻息肉发病机制中的作用。方法 用原位杂交的方法测定24例鼻息肉与8例下鼻甲的IL-15mRNA的表达情况,同时用免疫组化法检测其组织中Bcl-2及Bcl-XL的表达情况。结果 鼻息肉组中IL-15mRNA在黏膜下固有层浸润的以EOS为主的炎症细胞有很强的表达,与下鼻甲组IL-15mRNA的表达差异有统计学意义(P<0.05)。IL-15mRNA在多数鼻息肉中的黏膜下腺体上皮细胞有表达,且强于在下鼻甲组的表达。黏膜下固有层炎症细胞IL-15mRNA的表达与Bcl-XL的表达有相关性(r＝0.592)。结论 IL-15通过旁分泌或自分泌的方式作用于位于黏膜下固有层中以嗜酸性粒细胞为主的炎症细胞,并通过Bcl-XL途径诱导的凋亡抑制在鼻息肉的发病中可能起重要作用。IL-15在鼻息肉中黏膜下腺体的表达强于在下鼻甲中的表达,可能参与了鼻息肉形成过程中黏膜下腺体分泌功能紊乱的病理过程。     

Relationship between mucoceles, nasal polyposis and nasalisation

The etiology of sinus mucoceles remains somewhat obscure, but favorizing factors can be broadly divided in two: inflammation and trauma. Patients suffering from nasal polyposis offer a unique group for the study of mucoceles as they present the factor of inflammation related to their polyposis, and the factor of trauma when being treated surgically. In order to establish the relationship between nasal polyposis, mucoceles and nasalisation, we performed a retrospective study on the files of 501 patients operated according to the nasalisation technique. We then selected all the patients who also presented with a mucocele that could be diagnosed before, during or after the surgery. We also noted the presence of associated pathologies like bronchial asthma or the Fernand Widal's syndrome (Samter's triad), in order to see if they played a role in mucocele.formation. Our study group finally included 36 patients that presented one or several mucoceles in association with nasal polyposis. Only three of them did not have any antecedent of surgery or known trauma, giving an incidence of mucoceles associated to a non-surgically treated polyposis of 0.6%. The mean incidence rate of mucocele formation after nasalisation for nasal polyposis was estimated to be of 2.5/100 patients per year. The real incidence may be greater as some patients may have been lost in follow up. Sixteen patients presented multiple mucoceles. The most frequent location was the fronto-ethmoidal region. The formation of mucoceles, or their multiplicity, did not appear to be influenced by the presence of an associated pathology, as up to one half of the patients presented an isolated nasal polyposis. Nevertheless, when associated pathologies were present, mucoceles were more frequently observed in the Widal's triad. Most of the mucoceles were diagnosed during the first 6 years after nasalisation, with a peak incidence around year 2 and 3. We conclude that nasalisation, like other endonasal endoscopic techniques, can be related to a greater incidence of mucoceles than non-surgically treated nasal polyposis. Associated pathologies do not seem to influence mucoceleformation. It is important for the surgeon to follow-up patients operated of a nasal polyposis as mucoceles can develop very lately.