Cytokine and chemokine induction using cell wall component and toxin derived from gram-positive bacteria in the rat middle ear.

Lipoteichoic acid (LTA) is one of the components present within the cell wall layer of most gram-positive bacteria. It plays an important role in the initiation and progression of bacterial infection. In this study, we performed a rat middle ear and nasal perfusion with LTA purified from two different gram-positive bacterial species. Using ELISA and RT-PCR, the production and mRNA expression of rat chemokine, GRO/CINC-1, proinflammatory cytokine, TNF-alpha, in rat middle ear lavage and mucosa were investigated. GRO/CINC-1 in middle ear lavage was produced by stimulation of LTA in a time-dependent fashion; however, TNF-alpha production into the lavage was not detectable using ELISA assay. The mRNA expressions of GRO/CINC-1 and TNF-alpha in the middle ear mucosa were both induced after LTA and exotoxin exposures. The expression of IL-10 mRNA was also induced after 6 h of LTA and exotoxin exposures. The profile of the production of GRO/CINC-1 and TNF-alpha in rat nasal lavage was similar to that in the middle ear; however, the mRNA expressions of GRO/CINC-1, TNF-alpha and IL-10 in the nasal mucosa were different from those in the middle ear mucosa. These results suggest that the cell wall component and exotoxin of gram-positive bacteria can induce several cytokines in vivo and play an important role in the initiation of the inflammatory cascade in the middle ear.     

Histological investigations of the nasal mucosa in human fetuses

The adult nasal mucosa has been exposed to various external agents and selected physiological conditions. Changes in intranasal airflow influenced the morphological appearance of the mucosa. Studies of agents on the fetal mucosa and its development may contribute to better understanding of the morphology of the nasal mucosa. The authors studied the nasal mucosa of 20- to 26-week-old fetuses using light microscopy and scanning and transmission electron microscopy. Findings showed that this developing nasal mucosa took part in the production and movement of mucus in the nasal cavity.     

麻黄碱对鼻黏膜的影响及三磷酸腺苷对其治疗作用的探讨

目的:观察麻黄碱对健康Sprague-Dawley大鼠鼻黏膜形态、超微结构的影响,并探讨三磷酸腺苷(ATP)对它的干预作用。方法:健康Sprague-Dawley大鼠23只采用随机数字表法分为3组:对照组(A组),麻黄碱滴鼻组(B组),麻黄碱滴鼻加ATP腹腔注射组(C组)。于1、2、3、8周取鼻黏膜进行光镜和电镜观察。结果:B组用药第1、2、3周鼻黏膜的损害逐渐加重,3周后停药,第8周取材,观察损伤鼻黏膜形态没有恢复正常。C组用药第1周鼻黏膜几乎没有损伤,第2、3周鼻黏膜稍有损伤,3周后停用麻黄碱并续用ATP至第8周见损害鼻黏膜形态基本恢复正常。结论:麻黄碱可损伤健康Sprague-Dawley大鼠鼻黏膜,并随时间推迟而损伤程度加重,且损伤达到一定程度不可恢复;ATP可减轻麻黄碱对Sprague-Dawley大鼠鼻黏膜的损害,对麻黄碱引起的鼻黏膜损伤具有保护和治疗作用。     

In vitro expression of inducible nitric oxide synthase in the nasal mucosa of guinea pigs after incubation with lipopolysaccharides or cytokines

In order to demonstrate the involvement of nitric oxide synthases (NOS) – in particular the inducible isoform (iNOS) – in inflammatory processes within the nasal airways, we used organ-bath incubation to study isolated inferior turbinates and mucosa of the maxillary sinus of guinea pigs. The pattern of the expression in various substructures of the nasal mucosa was of special interest. Mucosa was incubated for 6 h with lipopolysaccharides (LPS) produced by E. coli, interleukin II (IL-2) or tumor necrosis factor-alpha (TNF-α). Saline was used as the control solution. Following incubation the specimens were fixed in buffered 4% formaldehyde solution over a period of 4 h. Tissues were next exposed to nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase-reaction and immunostained with specific antibodies to iNOS. Results then showed a clearly increased or initiated expression of iNOS in epithelium, glands, leucocytes and blood vessels of treated tissues in comparison to the control specimens. The inflammatory mediator LPS and the cytokines Il-2 or TNF-α alone were found to be capable of increasing the expression of iNOS, although the effects of LPS clearly exceeded those of the cytokines. This finding implicates iNOS-generated nitric oxide as a key factor for causing nasal swelling, secretion and obstruction during nasal infections and allergic episodes. Received: 18 November 1997 / Accepted: 22 April 1998     

鼻息肉组织中Th_1、Th_2细胞因子的表达及其意义

目的 :探讨 IL- 4、IL- 5等 8种细胞因子在鼻息肉发病中的作用和对鼻息肉治疗的意义。方法 :采用酶联免疫吸附实验 (EL ISA)法检测 2 5例鼻息肉患者鼻息肉组织中 Th1 细胞因子 IFN- γ、IL- 2、IL- 12和 Th2 细胞因子 IL- 4、IL- 5、IL- 8、IL- 10、IL- 13的表达 ,并比较经皮质激素治疗前后鼻息肉中细胞因子表达的差异。结果 :2 5例中 ,IL- 4、IL- 5、IL- 8、IL- 10、IL- 13等 Th2 细胞因子的表达较正常组织增高 ,其中以 IL- 4、IL- 5最为显著 ,分别达3.9倍和 8.8倍 ;应用皮质激素后细胞因子的表达水平显著降低 ,而 IFN- γ、IL- 2、IL- 12等 Th1 细胞因子浓度较正常组织中降低 ,应用激素后其表达无明显改变。结论 :Th2 细胞因子 IL- 4、IL- 5、IL- 8、IL- 10、IL- 13等的升高 ,在鼻息肉的发病过程中可能具有重要的意义 ,通过改变 Th2 细胞因子的表达趋势 ,可能对鼻息肉的治疗具有一定的意义。     

胸腺基质淋巴细胞生成素在变应性鼻炎小鼠鼻黏膜中的表达

目的探讨小鼠鼻腔黏膜中胸腺基质淋巴细胞生成素(thymic stromal lymphopoietin,TSLP)的含量及其分布。方法6周龄BALB/c小鼠经卵清蛋白(ovalbumin,OVA)致敏并激发制备变应性鼻炎模型,鼻腔激发第10天取鼻黏膜,进行HE染色观察黏膜组织形态,免疫组织化学染色观察TSLP的分布及定位,实时定量RT-PCR检测TSLP的含量。结果与对照组相比,实验组小鼠鼻黏膜上皮连续性破坏,固有层可见嗜酸性粒细胞浸润。对照组小鼠鼻黏膜中TSLP免疫反应阳性产物主要分布于上皮表面及固有层,染色较浅,实验组则较之明显深染。实时定量RT-PCR显示实验组小鼠鼻黏膜TSLP平均表达水平较对照组明显增高,表达量为其217.39倍。结论TSLP在变应性鼻炎小鼠鼻黏膜大量表达,在变应性鼻炎的发病中可能发挥重要作用。     

Decreased nasal mucosal sensitivity in older subjects

BACKGROUND: The sensitivity of the human nasal cavity mucosa to touch is not well understood. The site of receptors and mode of action responsible for the sensation of the nasal airflow is a topic of controversy. Previous studies have suggested that the skin-lined nasal vestibule is more sensitive to airflow than the mucosa of the nasal cavity. A possible decline in nasal sensitivity to airflow in older subjects has not been studied. METHODS: The threshold of the mucosal sensitivity to jets of air was assessed in 76 subjects with healthy nasal cavities. A total of 141 nostrils were tested, 67 in younger patients and 74 in older patients. RESULTS: Statistically significant (p < 0.001) increases in thresholds were found for all points tested for older patients compared with the younger patients. In general, the more sensitive locations were in the nasal vestibule. The nasal cavity mucosa in the inferior meatus was slightly more sensitive than the middle meatus. CONCLUSION: We have measured the threshold to touch (air jet sensitivity) in nine places in each of 141 nasal cavities and determined that the variability and sensitivity of these measurements among people varies by age and the distance from the nostril. Older subjects were found to have a higher threshold for the sensation of airflow, and the nasal vestibule was found to be more sensitive than the rest of the nasal cavity mucosa with the inferior meatus slightly more sensitive then the middle meatus.     

白细胞介素22治疗变应性鼻炎小鼠的实验研究

目的：探讨鼻腔局部给予重组小鼠白细胞介素22（IL-22）对小鼠变应性鼻炎免疫应答的调节作用。方法将24只6～8周的雌性BALB/c小鼠随机分为3组,每组8只,分别为对照组、模型组和IL-22组。以卵白蛋白（ovalbumin/OVA）为致敏原,氢氧化铝凝胶为佐剂制备变应性鼻炎小鼠模型,于激发前给予小鼠鼻腔局部滴注重组小鼠IL-22。观察小鼠变应性鼻炎症状改善情况,并检测三组小鼠鼻黏膜局部嗜酸性粒细胞侵袭情况、外周血清中OVA-特异性IgE（OVA-sIgE）浓度及Th1、Th2细胞因子的表达情况。结果重组小鼠IL-22干预的变应性鼻炎小鼠症状较模型组缓解,鼻腔黏膜局部嗜酸性粒细胞侵袭减少, OVA-sIgE浓度降低,Th2型细胞因子IL-4和IL-5浓度下降。差异均具有统计学意义（P〈0.05）。Th1型细胞因子IFN-γ浓度在IL-22治疗组和模型组间差异无统计学意义。结论鼻腔局部给予重组小鼠IL-22可以抑制变应性鼻炎小鼠的免疫反应,它有望成为治疗变应性鼻炎的一种新方法。     

IL-5和GM-CSF在慢性鼻-鼻窦炎手术前后鼻窦黏膜中的表达及意义

目的检测慢性鼻-鼻窦炎（chronic rhinosinusitis,CRS）手术前后鼻窦黏膜组织中白细胞介素-5（interleukin-5,IL-5）、粒细胞-巨噬细胞集落刺激因子（granulocyte-macrophage colonystimulating factor,GM-CSF）的表达,探讨IL-5、GM-CSF在CRS患者手术前后术腔黏膜转归过程的表达变化规律及其作用。方法采用ElivisionTMS-P免疫组织化学技术与HE染色方法检测10例行鼻内镜手术的Ⅱ型CRS患者术前,术后第1周、4～6周和8～10周鼻窦黏膜组织中IL-5和GM-CSF的表达;同时以1 0例单纯鼻中隔偏曲患者上颌窦口黏膜组织作为对照。结果①CRS患者术前,术后第1周、4～6周和8～10周鼻窦黏膜组织中IL-5和GM-CSF的表达水平均明显高于对照组（P〈0.01）。②CRS术后第1周IL-5和GM-CSF表达均较术前明显降低（P〈0.01）;术后第4～6周IL-5和GM-CSF的表达达高峰,术后第8～10周IL-5和GM-CSF的表达下降。结论IL-5和GM-CSF在Ⅱ型CRS患者术前、术后鼻窦黏膜组织中表达呈一定的规律变化,提示IL-5和GM-CSF可能与CRS病变的转归有密切关系。     

Hypoxia stimulates inflammatory and fibrotic responses from nasal-polyp derived fibroblasts

OBJECTIVES/HYPOTHESIS: Chronic sinusitis is primarily an inflammatory disorder characterized by hyperplasia of immune cells and sinus tissue. Nasal mucosal swelling or polyps can occlude the sinus ostia, decreasing the level of oxygen available to the sinus tissue. Hypoxia in many diseases results in increased recruitment of inflammatory cells and release of cytokines. The role of hypoxia in chronic sinusitis is unknown. We hypothesized that hypoxia induces production of mediators that recruit cells into the sinus tissue and are involved in remodeling of the nasal mucosa. METHODS: We compared data from unstimulated nasal-polyp derived fibroblasts with those cultured in hypoxic (10% O2) and anoxic (0% O2) environments. Changes in mRNA expression and protein levels of cytokines and chemokines were measured along with changes in cellular proliferation. RESULTS: Hypoxic conditions did not change the proliferative capacity of fibroblasts, whereas anoxia led to a 40% reduction in cellular proliferation (P < .05). Hypoxia led to increases in secretion of many cytokines including vascular endothelial growth factor and CCL11. As a marker of remodeling, procollagen and fibronectin production were significantly increased under hypoxic conditions. CONCLUSIONS: Hypoxic conditions present in the sinus tissue could increase production of proinflammatory and remodeling cytokines that contribute to the inflammation observed in sinusitis. Surgical intervention may help decrease inflammation by allowing reoxygenation of the sinus cavity and decrease the hypoxic induction of cytokines and remodeling factors.     

白细胞型12-酯氧合酶在变应性鼻炎大鼠模型鼻黏膜中的表达

目的 研究白细胞型12-酯氧合酶(leukocytetype 12-lipoxygenase,L-12-LO)在变应性鼻炎(AR)大鼠鼻黏膜中的表达.方法 在健康SD大鼠腹腔注射卵清蛋白和AI(OH)3混合液,然后鼻腔滴人5%卵清蛋白液,建立AR动物模型.用免疫组化SABC法检测L-12-LO在AR鼻黏膜中的表达.结果...     

Leukotriene receptor antagonist pranlukast suppresses eosinophil infiltration and cytokine production in human nasal mucosa of perennial allergic rhinitis

The purpose of this study was to investigate the influence of pranlukast on eosinophilic inflammation and cytokine production in human nasal mucosa. Twelve patients were treated with pranlukast, and samples were obtained from the nasal mucosa of the inferior turbinate. With respect to cell infiltration, a significant decrease was observed in the percentage of inflammatory cells (secreted eosinophil cationic protein [EG2] and neutrophil elastase) after treatment. The levels of cytokines and chemical mediators (interleukin [IL]-4, IL-5, RANTES [regulated on activation, normal T cell expressed and secreted], cysteinyl leukotrienes, IL-1beta, tumor necrosis factor-alpha, and IL-8) assessed by enzyme-linked immunosorbent assay and enzyme immunoassay were significantly decreased. These results indicate that pranlukast decreased the levels of a majority of the cytokines in nasal mucosa, leading to improvement in subjective nasal symptoms. Furthermore, these results support the hypothesis that pranlukast exerts its therapeutic action primarily by blocking the leukotriene receptors on eosinophils.     

吸入二氧化硫对小鼠变应性鼻炎的影响

OBJECTIVE: To observe the effect of sulphur dioxide (SO2) inhalation on the pathogenesis of allergic rhinitis (AR) in mice, and investigate the toxic effect of SO2 on respiratory tract mucosa. METHODS: Fifty male Kunming strain mice were randomly allocated to five groups, i. e., control group, AR group and AR plus different concentrations of SO2 group (three sub-groups). Nasal cavity irrigating solution was gathered from nasal cavity, and blood from the orbital venous sinus after anesthesia The concentrations of IL-5 and IL-13 in the peripheral serum and nasal cavity irrigating solution were measured by ELISA. The number of eosinophils (EOS) per square millimeter in sinus mucosa was calculated by hematoxlin-eosin. The expression of SP-D in nasal mucosa was analyzed by immunohistochemistry technique. RESULTS: With increasing concentrations of SO2, the levels of IL-5 and IL-13 in the peripheral serum, and the density of Eos in sinus mucosa increased simultaneously. A positive correlation existed between the concentration of inhaled SO2 and the elevation of both IL-5, IL-13 and Eos infiltration in nasal mucosa. The coefficient correlation relatively were 0.894, 0.874, 0.894, 0.891 and 0.870 (P <0.01). The expression of SP-D in 56 mg/m3 and 112 mg/m3 SO2 groups was higher, while it was lower in 168 mg/m3 SO2 group (P < 0. 001). CONCLUSIONS: The study showed that sulphur dioxide inhalation facilitates the onset of allergic rhinitis in mice. SO2-related Th2-derived cytokines as well as the infiltration of EOS in nasal mucosa help to aggravate the development of allergic rhinitis.     

Rat model of platelet-activating factor-induced rhinosinusitis

Platelet-activating factor (PAF) is known to be a potent inflammatory mediator, especially in allergic inflammation. However, the exact role of PAF in the pathogenesis of rhinosinusitis has not been clearly established. To understand the role of PAF in the pathogenesis of rhinosinusitis, it is necessary to develop an animal model of PAF-induced rhinosinusitis. The aim of this study was to develop a rat model of rhinosinusitis induced by intranasally applied PAF. Fifty microliters of 16 microg/mL PAF was applied intranasally through each naris in 4-week-old Sprague-Dawley rats, and the same amount of vehicle was applied in control rats. At 1, 3, or 5 days, the animals were painlessly sacrificed, and the nasal cavity and sinuses were prepared for histologic investigation. The histologic sections were examined in a blind manner for the appearance of neutrophil clusters in the sinonasal air space, and the numbers of eosinophils, areas of epithelial loss, goblet cells, and inducible nitric oxide synthase (iNOS)-positive inflammatory cells in the mucosa. Neutrophil clusters were observed in the air space, and the number of eosinophils, areas of epithelial loss, goblet cells, and iNOS-positive inflammatory cells in the mucosa were increased significantly in the PAF-applied rats. The amount of inflammation varied according to the time interval, showing a peak at day 3. We conclude that intranasally applied PAF induces rhinosinusitis in rats. The histologic evidence of rhinosinusitis revealed the appearance of neutrophil clusters in the sinonasal air space, infiltration of eosinophils and iNOS-positive inflammatory cells in the mucosa, areas of epithelial loss, and goblet cell hyperplasia in the epithelium. This rat model of PAF-induced rhinosinusitis may be applied for better understanding of the role of PAF in the pathogenesis of rhinosinusitis.     

吸入二氧化硫对小鼠变应性鼻炎的影响

目的 观察二氧化硫(sulphur dioxide,SO2)对小鼠变应性鼻炎(AR)的影响,探讨SO2对鼻黏膜的毒性作用机理.方法 纯系雄性昆明小鼠50只,随机分为对照组、AR组和3个SO2吸入组(在AR基础七吸入不同剂量的SO2),共5组,每组10只.收集各组小鼠鼻腔灌洗液和外周血,采用间接酶联免疫吸附试验法(ELISA)检测血清和鼻腔灌洗液中自细胞介素5(IL-5)和白细胞介素13(IL-13)的水平;常规HE染色观察鼻窦黏膜中嗜酸粒细胞的浸润情况;免疫组化染色分析鼻窦黏膜中表面活性蛋白D(surfactant protein D,SP-D)的表达.结果 随着吸入SO2剂量的增加,血清和鼻腔灌洗液中IL-5、IL-13的水平增高,鼻窦黏膜中嗜酸粒细胞的浸润增多,且均呈正相关(r值分别为0.894、0.874、0.894、0.891及0.870,P值均＜0.01).56 mg/m3和112 mg/m3 SO2吸入组鼻窦黏膜中SP-D的表达随着吸入SO2浓度的增高而增强,而168 mg/m3 SO2吸入组中SP-D的表达反而降低(P＜0.001).结论 鼻腔吸入的SO2可以促进Th2细胞因子表达,增加鼻黏膜嗜酸粒细胞浸润,在一定程度上加重AR病变.     

放射性鼻黏膜损伤后组织纤维化重塑的特点

目的 探讨鼻黏膜纤维化在放射性鼻黏膜损伤中的作用.方法 清洁级SD大鼠72只,雄性,随机分为两组,空白对照组36只,予以假照射;辐射损伤组36只,予以X射线局部照射,总辐射剂量40 Gy.损伤组分别于辐射完成后1周、2周、4周、8周、3个月和6个月(每个时间点各6只大鼠)配对处死大鼠,取出中鼻甲子以扫描和透射电镜观察,苏木素-伊红(hematoxylin-eosin,HE)染色;阿辛蓝-过碘酸-希夫(alcian blue-periodic acid-SclIif,AB-PAS)染色,Masson三色胶原染色(Masson trichrome,MT)法染色,观察鼻黏膜组织病理变化;化学比色法测定鼻黏膜羟脯氨酸(Hyp)的含量.结果 辐射损伤后,早期(4周内)主要以急性炎性反应为特点,4周后修复开始,6个月时修复基本结束.受照后1周,大鼠鼻黏膜中出现胶原沉积,胶原沉积量随着时间的推移而进行性增多.结论 照射能引起鼻黏膜组织一系列的病理改变,鼻黏膜纤维化可能是放射性鼻黏膜损伤迁延不愈的重要原因之一.     

Fungal cultures of different parts of the upper and lower airways in chronic rhinosinusitis

The relation between fungi, upper and lower airways in chronic rhinosinusitis (CRS) patients are not clear yet. So the aim of this study was to identify the different cultured fungi in various sub-sites of the nasal cavity and lower airways in adult (CRS) patients and to correlate the cultured fungi to the associated cellular inflammatory changes. In the outpatient clinic a control group of 10 normal subjects was subjected to total nasal lavages to validate our mycological culture technique. Twenty-five adult CRS patients were enrolled in this prospective study. Under general anaesthesia before functional endoscopic sinus surgery (FESS) operation 50 nasal vestibular swabs, 25 bronchoalveolar lavages (BALs), 50 middle meatal lavages (MMLs) and 50 nasal cavity lavages (NCLs) were obtained in the operating room. These samples were processed for fungal culture and eosinophilic cellular counts. The intraoperative pathological specimens were examined using Haematoxylin and Eosin (H&E) and Gomori methanamine silver (GMS) staining. In the normal control group total nasal lavages showed 100% positive fungal cultures. In the CRS patient group the BALs showed positive fungal cultures in 28%. Nasal vestibule cultures were positive in 8%. Positive middle meatal cultures were obtained in 44% of the 25 CRS patients. Two cases (8%) with maxillary fungal ball showed a positive maxillary sinus culture but a negative middle meatal culture. Nasal cavity lavages were positive in 36%. Middle meatal eosinophilia was identified in 33.6% of the positive middle meatal fungal culture. Following the deShazo's criteria of diagnosis of allergic fungal rhinosinusits (AFRS), only 16% of the subjects in this study fulfilled the criteria. No correlation existed between fungal culture, cellular and other clinical parameters. Also no correlation existed between upper and lower airway positive cultures. In conclusion fungi seemed to be present in different percentages and types in different sub sites of the airways but without associated eosinophilia. There were no significant correlations between the fungal culture and clinical parameters of CRS nor were there significant correlations between fungal culture and objective lower airway involvement.     

三种促炎因子在鼻息肉及术后两周紧邻术区鼻黏膜的变化

目的 研究鼻息肉及鼻内镜术后2周紧邻术区鼻黏膜中血管细胞黏附分子（vascular cell adhesion molecule，VCAM）-1、嗜酸粒细胞亲合素（Eotaxin）及血管内皮生长因子（vascular endothelial growth factor，VEGF）的表达及相关性，探讨鼻息肉术后复发的可能机制。方法 应用链霉亲和素-过氧化物酶（SABC）免疫组化法检测30例鼻息肉及其中22例鼻内镜术后2周患者紧邻术区鼻黏膜的VCAM-1、eotaxin和VEGF的表达情况；HE染色光镜下观察组织结构、炎性细胞浸润情况。结果 ①HE染色可见鼻息肉组织嗜酸粒细胞大量浸润，术后则明显减少（t=2．891，P〈0．05）；②VCAM-1在鼻息肉手术前后均呈阳性表达，阳性面积差异无统计学意义（t=-2．051，P〉0．05），平均吸光度术后减弱（t=3．670，P=0．05）；Eotaxin手术前后阳性面积差异无统计学意义（t=0．739，P〉0．05），平均吸光度术后明显减弱（t=4．428，P〈0．05），Eotaxin术后腺体阳性率明显增加（t=-2．899，P〈0．05）；③VEGF阳性面积及平均吸光度手术前后表达差异均无统计学意义（t值分别为-0．037、0．825，P值均〉0．05）。结论 ①鼻息肉鼻内镜手术后嗜酸粒细胞数量明显减少，说明紧邻术区水肿状组织不同于鼻息肉。②VCAM-1、Eotaxin术后紧邻术区鼻黏膜阳性表达，说明Eotaxin有可能上调VCAM-1在血管内皮的表达，促进嗜酸粒细胞黏附于内皮细胞，穿内皮细胞问隙迁移到组织中，可能是息肉复发的基础。其中Eotaxin术后腺体阳性表达明显增加，推测其可能在鼻息肉复发早期发挥重要作用。③VEGF术后高表达，提示VEGF可促进术区血管增生及通透性增强，使局部组织增生、水肿，从而可能成为息肉复发过程中的重要因素之一。     

Proinflammatory cytokines in allergic rhinitis

Allergic diseases such as allergen-induced rhinitis represent an inflammatory reaction that is characterized by the chemotaxis and activation of various cell populations. A high degree of cell-to-cell communication is needed to orchestrate this inflammatory immune response. A variety of cytokines and adhesion receptors seem to play an important role in the allergic late phase reaction. Here we demonstrate that proinflammatory cytokines such as interleukin(IL)-1, IL-8 and TNF-α (tumor necrosis factor-alpha) can be detected in nasal secretions and mucosa by enzyme-linked immunosorbent assay and immunohistochemistry. The increased expression of adhesion receptors in mucosa specimens of patients with seasonal allergic rhinitis points to their role in regulating the cellular migration and probably represents a key event in allergic inflammation. We established an in vitro model using freshly taken nasal mucosa to study the induction of adhesion receptors by proinflammatory cytokines. E-selectin, an endothelial receptor, was strongly upregulated by IL-1β, TNF-α and allergen. The induction due to allergen exposure of the mucosa was markedly inhibited by soluble cytokine receptors (sIL-1R, TNF-BP) or by a receptor antagonist (IL-Ira) and prednisolone, These findings indicate that proinflammatory cytokines may be key factors for the upregulation of adhesion processes in human nasal mucosa and the activation of various cell populations involved in the allergic inflammation. They therefore represent a main target for new therapeutic strategies.