Regulatory B Lymphocytes Colonize the Respiratory Tract of Neonatal Mice and Modulate Immune Responses of Alveolar Macrophages to RSV Infection in IL-10-Dependant Manner.

Respiratory syncytial virus (RSV) is the prevalent pathogen of lower respiratory tract infections in children. The presence of neonatal regulatory B lymphocytes (nBreg) has been associated with a poor control of RSV infection in human newborns and with bronchiolitis severity. So far, little is known about how nBreg may contribute to neonatal immunopathology to RSV. We tracked nBreg in neonatal BALB/c mice and we investigated their impact on lung innate immunity, especially their crosstalk with alveolar macrophages (AMs) upon RSV infection. We showed that the colonization by nBreg during the first week of life is a hallmark of neonatal lung whereas this population is almost absent in adult lung. This particular period of age when nBreg are abundant corresponds to the same period when RSV replication in lungs fails to generate a type-I interferons (IFN-I) response and is not contained. When neonatal AMs are exposed to RSV in vitro, they produce IFN-I that in turn enhances IL-10 production by nBreg. IL-10 reciprocally can decrease IFN-I secretion by AMs. Thus, our work identified nBreg as an important component of neonatal lungs and pointed out new immunoregulatory interactions with AMs in the context of RSV infection.

Differential expression and role of S100 proteins in chronic rhinosinusitis.

PURPOSE OF REVIEW: Immune system modulators have been under investigation to help elucidate the underlying pathophysiologies of chronic rhinosinusitis (CRS). Psoriasin (S100A7) and calgranulins (S100A8, S100A9, and S100A12) are S100 proteins that have been studied for their immune-mediating responses to pathogens within the context of CRS. This review highlights the expression patterns and proposed roles of S100 proteins in CRS with (CRSwNP) and without (CRSsNP) nasal polyps. RECENT FINDINGS: Elevated levels of S100A7 and S100A12 were measured in the sinonasal tissues of patients with CRSsNP compared with CRSwNP and controls. S100A12 expression in CRSsNP was significantly correlated to disease severity. Contrastingly, increased S100A8, S100A9, and S100A8/A9 levels were demonstrated in the nasal polyp tissues of patients with CRSwNP compared with those in inferior turbinate and uncinate tissues of patients with CRSsNP and controls. SUMMARY: The reported differential expression patterns and activities of psoriasin and calgranulins suggest that S100 proteins exert unique and concerted roles in mediating immunity in different subtypes of CRS. These studies will enable further investigations focused on understanding the immune-modulating mechanisms of S100 proteins in different inflammatory signaling pathways and disease phenotypes of CRS toward the pursuit of identifying new biomarkers and targets for improved outcomes.

Turbinate-Specific IgE in Normal and Rhinitic Patients.

BACKGROUND: Specific immunoglobulin E (sIgE) within the nasal airway is likely to be the most ideal marker of allergic status, but little is known of the normative values in asymptomatic patients and those with rhinitis. OBJECTIVE: The aim of this study was to assess the diagnostic characteristics of inferior turbinate tissue biopsy sIgE in asymptomatic and rhinitic patients. METHODS: A diagnostic cross-sectional study was undertaken, involving patients who underwent inferior turbinate surgery with or without other surgical interventions. Inferior turbinate tissue biopsy was performed during surgery and was assessed for allergen sIgE (dust mite, grass [temperate or subtropical], and animal epithelium) using an automated immunoassay. Tissue sIgE was assessed among asymptomatic patients and those with nasal symptoms. Data were presented as median (interquartile range). A receiver operating curve was used to predict the diagnostic utility of turbinate tissue sIgE in determining allergic rhinitis. RESULTS: A total of 160 patients (41.89 ± 14.65 years, 36.9% females) were included. The median tissue sIgE concentration among the asymptomatic nonatopic group of patients was 0.09 (0.08-0.10) kUA/L and tissue sIgE > 0.10 kUA/L was determined as a positive threshold. Inferior turbinate tissue sIgE was shown to be a predictive test for allergic rhinitis (area under curve: 0.87, 95% confidence interval: 0.84-0.90) with 90% sensitivity and 89% negative predictive value. CONCLUSION: Inferior turbinate tissue biopsy sIgE is a sensitive tool to predict allergic rhinitis. The threshold value of 0.1 kUA/L corresponded well with the asymptomatic nonatopic group of patients. This method detects sIgE in the nasal mucosa and may be a useful test for allergic rhinitis in future research.

Characteristics of Human Turbinate-Derived Mesenchymal Stem Cells Are Not Affected by Allergic Condition of Donor.

The characteristics of mesenchymal stem cells (MSCs) derived from human turbinates (hTMSCs) have not been investigated in allergic rhinitis. We evaluated the influence of allergic state of the donor on the characteristics, proliferation, and differentiation potential of hTMSCs, compared with hTMSCs derived from non-allergic patients. hTMSCs were isolated from five non-allergic and five allergic patients. The expression of toll-like receptors (TLRs) in hTMSCs was measured by FACS, and cell proliferation was measured using a cell counting kit. Cytokine secretion was analyzed using multiplex immunoassays. The osteogenic, chondrogenic, and adipogenic differentiation potentials of hTMSCs were evaluated by histology and gene expression analysis. In allergic patients, FACS analysis showed that TLR3 and TLR4 were more highly expressed on the surface of hTMSCs than TLR2 and TLR5. The proliferation of hTMSCs was not influenced by the presence of TLR priming. The expression of IL-6, IL-8, IL-12, IP-10, and RANTES was upregulated after the TLR4 priming. The differentiation potential of hTMSCs was not influenced by TLR priming. These characteristics of hTMSCs were similar to those of hTMSCs from non-allergic patients. We conclude that the allergic condition of the donor does not influence TLR expression, proliferation, or immunomodulatory potential of hTMSCs.

Late production of CXCL8 in ruminant oro-nasal turbinate cells in response to Chlamydia abortus infection.

Chlamydia abortus is an obligate intracellular bacterium that is an important cause of ovine abortion worldwide. There are reports of abortions in cattle, but these are very rare compared to the reported incidence in sheep. The bacterium is transmitted oro-nasally and can establish a sub-clinical infection until pregnancy, when it can invade the placenta and induce an inflammatory cascade leading to placentitis and abortion. Early host-pathogen interactions could explain differential pathogenesis and subsequent disease outcome in ruminant species. In this study, we assessed the ability of sheep and cattle oro-nasal turbinate cells to sense and respond to C. abortus infection. The cells expressed toll like receptor (TLR) 2, TLR4, nucleotide oligomerization domain (NOD) 1 and NOD-like receptor pyrin domain containing 3 (NLRP3) mRNA. In response to C. abortus infection, both ovine and bovine turbinate cells produce CXCL8 mRNA and protein late in the bacterial developmental cycle, but do not produce IL-1ß or TNF-α. The UV-inactivated bacteria did not elicit a CXCL8 response, suggesting that intracellular multiplication of the bacteria is important for activating the signalling pathways. The production of innate immune cytokines from cattle and sheep turbinate cells in response to C. abortus infection was found to be largely similar.

Clinical effects of middle turbinate resection after endoscopic sinus surgery: a systematic review.

BACKGROUND: The middle turbinate (MT) is a structure that is often carefully preserved during endoscopic sinus surgery (ESS) in an effort to preserve nasal physiology and serve as an anatomic landmark. However, resection is performed in select cases because of involvement of the MT in the inflammatory process, obstruction, or instability. Therefore, significant controversy exists among surgeons regarding the indications for proceeding with MT resection in ESS. This study evaluates clinical outcomes of MT resection after ESS. METHODS: An English language search of the PubMed and Ovid databases was conducted for publications examining clinical outcomes of MT resection after ESS performed for chronic rhinosinusitis. Two authors independently examined the articles to identify those meeting inclusion criteria. Any differences over which studies to include were resolved by discussion and consensus. Bias assessment was conducted using the Cochrane Collaboration bias tool for randomized controlled trials and the Newcastle-Ottawa bias tool for cohort and case-control studies. RESULTS: After initial screening, search results revealed 71 articles that warranted detailed evaluation. After applying inclusion criteria, 9 studies were selected. A total of 2123 patients were included among the studies. All studies were controlled. Within the limited available data, olfaction scores may be improved in the MT resection patients compared with MT preservation patients. No difference between the groups was noted for quality of life outcomes, nasal airway resistance, or rates of postoperative frontal sinusitis. In regard to postoperative endoscopic examinations, some studies note greater improvement in the MT resection group compared with the MT preservation group, while others were equivalent. CONCLUSION: Although some studies show outcome benefit in MT resection patients compared with MT preservation patients, several others show no difference. When MT resection was appropriately indicated, no studies showed detrimental effects compared with MT preservation in their designated outcomes. Additional more stringent studies are warranted.

Comparison of the histologic changes in conchae induced by radiofrequency thermal ablation and submucosal diathermy.

Objective of study was to determine the histological change induced in the conchae by submucosal diathermy and radiofrequency thermal ablation, two techniques used in the treatment of lower conchal hypertrophy, and to compare the two methods to each other. The study was performed on 15 rabbits. Radiofrequency was applied to the study animals in Group I (n = 5) and submucosal diathermy to Group II (n = 5), while Group III (n = 5) was the untreated control. The animals were decapitated 21 days after treatment and their conchae nasales ventrales excised on both sides. Histology slides were prepared and evaluated by light microscopy for ciliary loss, increase in submucosal vascularity, loss of goblet cells, inflammatory cellular infiltration, fibrosis and epithelial damage. The differences between Groups I and III were not significant regarding ciliary loss, increase in submucosal vascularity, loss of goblet cells and epithelial damage (p > 0.05), while the inflammatory cellular infiltration and fibrosis were significantly different between these groups (p < 0.05). As for the differences between Groups II and III, they were significant for each of the compared parameters (p < 0.05), while among Groups I and II they were significant for ciliary loss (p < 0.05), increase in submucosal vascularity, loss of goblet cells, inflammatory cellular infiltration and epithelial damage but not fibrosis (p > 0.05). Based on these findings, we can state that the use of radiofrequency thermal ablation causes less change in the normal conchal histology than submucosal diathermy application.

The role of nasal cytology in the management of inferior turbinate hypertrophy.

Inferior turbinate hypertrophy (ITH) is the main cause of nasal obstruction symptom. This study aimed at investigating whether a particular cellular pattern could be a predictive factor for failure of medical treatment for ITH in patients with rhinitis. Globally, 258 patients with chronic nasal obstruction due to ITH were evaluated by: visual analogue scale assessment of symptoms, skin prick tests, fiber-endoscopy, active anterior rhinomanometry, and nasal cytology. All patients were treated with drugs for 3 months and then re-evaluated. The symptom improvement depended on the different cellular pattern. There was improvement in: 54 (51.4 percent) patients with allergic rhinitis, 72 (69.2 percent) with non-allergic rhinitis with neutrophils (NARNE), 15 (42.8 percent) with non-allergic rhinitis with eosinophils (NARES), and 9 (64.3 percent) with non-allergic rhinitis with mast cells/non-allergic rhinitis with eosinophils and mast cells (NARMA/NARESMA). The non-responders (108; 41.9 percent) were therefore directed towards surgical treatment. Both patients with allergic rhinitis and patients affected by NARES had a higher failure rate to medical treatment compared with NARMA and NARESMA groups (pless than0.01). In conclusion, elevated number of eosinophils, in the nasal secretion of both allergic (allergic rhinitis) and non-allergic (NARES) patients with ITH, can be associated to a higher medical treatment failure rate.

Detecting local immunoglobulin E from mucosal brush biopsy of the inferior turbinates using microarray analysis.

BACKGROUND: It has been previously demonstrated that local, antigen-specific immunoglobulin E (IgE) can be detected using a standard in vitro assay of lysed epithelial cells in saline, harvested via nasal mucosal brush biopsy (MBB). However, compared to surgical biopsy or serum, smaller amounts of IgE are harvested using MBB, making detection much more difficult. Microarray analysis (MA) requires less IgE for detection, making this an attractive option for MBB. The goals of this study were to compare MA to a standard IgE assay for detecting antigen-specific IgE from MBB and to test the association between the presence of multiple positive components on MA with specific IgE on standard assay and skin-prick testing (SPT) grade. METHODS: MBB samples from 18 allergic rhinitis patients, which were previously tested for antigen-specific IgE to common airborne allergens using a standard IgE assay, underwent MA for antigen-specific IgE to multiple components of airborne and food allergens. Fisher's exact probability testing was used to measure the strength of association between the 2 testing modalities for Timothy grass, ragweed, cat, Alternaria, and D. farinae. RESULTS: MA correlated very highly with standard assay (p < 0.0001) and 50% of positive antigens on MA detected multiple components to that antigen. The presence of multiple components was not associated with specific IgE levels on standard assay or SPT grade. CONCLUSION: This is the first demonstration that antigen-specific IgE in saline samples can be measured using MA. The ability of MA to measure smaller amounts of IgE, with similar accuracy, may give it a potential advantage for MBB analysis in the future.

Antigen-specific activities of CD8+ T cells in the nasal mucosa of patients with nasal allergy.

BACKGROUND: The prevalence of chronic rhinitis is increasing rapidly. Its pathogenesis is not fully understood but immune inflammation is one plausible causative factor. Antigen specific CD8+ T cells play a critical role in the induction of chronic inflammation. This study aims to investigate the role of antigen specific CD8+ T cells in the pathogenesis of chronic AR. METHODS: Nasal mucosal epithelial samples obtained by the surface of the nasal mucosaof patients with AR complicated with inferior turbinate hypertrophy. Exosomes were purified from the scratching samples and examined by immune gold electron microscopy. Cell culture models were employed to evaluate the effect of exosomes on modulating CD8+ T cell activity. RESULTS: Exosomes purified from patients with chronic AR carried microbial products, Staphylococcal enterotoxin B (SEB), and airborne antigen, Derp1. Dendritic cells pulsed by SEB/Derp1-carrying exosomes showed high levels of CD80, CD86 and the major histocompatibility class I (MHCI). Exosome-pulsed dendritic cells could induce naive CD3+ T cells to differentiate into CD8+ T cells. Upon exposure to a specific antigen, the CD8+ T cells released granzyme B and perforin and more than 30% antigen specific CD8+ T cells proliferated. CONCLUSIONS: Antigen specific CD8+ T cells play an important role in the pathogenesis of chronic AR complicated with inferior turbinate hypertrophy.

Nasal endoscopy in children with suspected allergic rhinitis.

OBJECTIVES/HYPOTHESIS: Ear, nose, and throat assessment may be frequently requested for children with allergic rhinitis (AR). Nasal endoscopy allows a thorough evaluation of the nose. The aim of the study was to investigate whether there are endoscopic signs predictive for AR diagnosis in a cohort of children with suspected AR. STUDY DESIGN: Cohort of observational study. METHODS: There were 176 children (99 males; mean age, 7.5 years) studied. Clinical visit, nasal endoscopy, and skin prick test were performed in all patients. Nasal endoscopic signs were pale turbinates, middle turbinate contact, and inferior turbinate contact. The AR diagnosis was made when nasal symptom history was concordant with sensitization. RESULTS: AR was diagnosed in 141 children. Inferior and middle turbinate contact were reliable predictive factors for AR (odds ratio 5.38 and 3.42, respectively), whereas pale turbinates did not predict it. CONCLUSIONS: This study suggests that nasal endoscopy may reveal signs predictive for AR diagnosis in children.

The airway antigen sampling system: respiratory M cells as an alternative gateway for inhaled antigens.

In this study, we demonstrated a new airway Ag sampling site by analyzing tissue sections of the murine nasal passages. We revealed the presence of respiratory M cells, which had the ability to take up OVA and recombinant Salmonella typhimurium expressing GFP, in the turbinates covered with single-layer epithelium. These M cells were also capable of taking up respiratory pathogen group A Streptococcus after nasal challenge. Inhibitor of DNA binding/differentiation 2 (Id2)-deficient mice, which are deficient in lymphoid tissues, including nasopharynx-associated lymphoid tissue, had a similar frequency of M cell clusters in their nasal epithelia to that of their littermates, Id2(+/-) mice. The titers of Ag-specific Abs were as high in Id2(-/-) mice as in Id2(+/-) mice after nasal immunization with recombinant Salmonella-ToxC or group A Streptococcus, indicating that respiratory M cells were capable of sampling inhaled bacterial Ag to initiate an Ag-specific immune response. Taken together, these findings suggest that respiratory M cells act as a nasopharynx-associated lymphoid tissue-independent alternative gateway for Ag sampling and subsequent induction of Ag-specific immune responses in the upper respiratory tract.

Different regulation of cigarette smoke induced inflammation in upper versus lower airways.

BACKGROUND: Cigarette smoke (CS) is known to initiate a cascade of mediator release and accumulation of immune and inflammatory cells in the lower airways. We investigated and compared the effects of CS on upper and lower airways, in a mouse model of subacute and chronic CS exposure. METHODS: C57BL/6 mice were whole-body exposed to mainstream CS or air, for 2, 4 and 24 weeks. Bronchoalveolar lavage fluid (BAL) was obtained and tissue cryosections from nasal turbinates were stained for neutrophils and T cells. Furthermore, we evaluated GCP-2, KC, MCP-1, MIP-3alpha, RORc, IL-17, FoxP3, and TGF-beta1 in nasal turbinates and lungs by RT-PCR. RESULTS: In both upper and lower airways, subacute CS-exposure induced the expression of GCP-2, MCP-1, MIP-3alpha and resulted in a neutrophilic influx. However, after chronic CS-exposure, there was a significant downregulation of inflammation in the upper airways, while on the contrary, lower airway inflammation remained present. Whereas nasal FoxP3 mRNA levels already increased after 2 weeks, lung FoxP3 mRNA increased only after 4 weeks, suggesting that mechanisms to suppress inflammation occur earlier and are more efficient in nose than in lungs. CONCLUSIONS: Altogether, these data demonstrate that CS induced inflammation may be differently regulated in the upper versus lower airways in mice. Furthermore, these data may help to identify new therapeutic targets in this disease model.

Localized immunoglobulin E expression in allergic rhinitis and nasal polyposis.

PURPOSE OF REVIEW: This article reviews recent literature on local tissue identification of immunoglobulin E (IgE) in various sinonasal inflammatory conditions. Discussions of local IgE expression in allergic and nonallergic rhinitis, atopic and nonatopic sinonasal polyposis, and allergic fungal rhinosinusitis are included. RECENT FINDINGS: Increased levels of IgE and positive reactivity on nasal allergen provocation tests have been demonstrated in nasal lavage fluid of patients with negative systemic allergy testing. In addition, elevated levels of Alternaria alternata-specific IgE have been identified in nasal polyp patients; this is hypothesized as a contributory factor in the development of nasal polyposis. Further evidence supports the role of local IgE to Staphylococcus aureus superantigens in atopic and nonatopic nasal polyposis. Finally, local IgE specific for a range of antigens has been identified in sinus and inferior turbinate tissue in patients with allergic fungal rhinosinusitis. SUMMARY: Increased levels of IgE have been identified in sinonasal tissues in allergic and nonallergic rhinitis, atopic and nonatopic sinonasal polyposis, and allergic fungal rhinosinusitis. The ability to identify local tissue IgE in inflammatory sinonasal disease states may have significant diagnostic and therapeutic implications.

Cytochrome P4502A6 stability in a mini organ culture model of human nasal mucosa for genotoxicology studies as detected by flow cytometry.

Three dimensional mini organ cultures (MOCs) of human nasal turbinate epithelia have been shown to be a relevant tool in genotoxicology studies. MOCs allow repetitive or chronic exposure of cells in an organ specific mucosal architecture for an extended period of time and monitoring of possible adverse effects with, e.g., the comet assay. It is the aim to demonstrate whether the proteins of key enzymes of xenobiotic metabolism, represented by cytochrome P450 2A6 (CYP2A6), remain on a stable level for a culture period that allows repetitive or chronic exposure to xenobiotics. Culture of mini organs was performed by cutting pieces of 1 mm(3) from fresh specimens of human nasal turbinates. MOCs of five tissue donors were incubated on multi-well plates with BEBM, on days 0, 4, 7, 9, and 11 aliquots were transmitted to flow cytometric quantification of the CYP2A6 protein. The CYP2A6 protein could be demonstrated on all days of culture investigated. Interindividual differences were more pronounced on day 0 than at later stages of culture. Although there appeared to be a slight decrease over the culture period, flow cytometric analysis did not reveal a significant loss of the signals up to day 11. The present data could show a pre-requisite of metabolic competence of MOCs that is in contrast to single cell cultures. Thus, this type of organ culture provides an in vitro model suitable for the assessment of genotoxic effects of environmental pollutants mimicking the in vivo situation with target cells of carcinogens in their functional organ specific architecture.

Chitosan microspheres containing Bordetella bronchiseptica antigens as novel vaccine against atrophic rhinitis in pigs.

The immune-stimulating activities of Bordetella bronchiseptica antigens containing dermonecrotoxin (BBD) loaded in chitosan microspheres (CMs) have already been reported in vitro and in vivo with a mouse alveolar macrophage cell line (RAW264.7) and mice. Therefore, this study attempted to demonstrate the successful induction of mucosal immune responses after the intranasal administration of BBD loaded in CMs (BBD-CMs) in colostrum-deprived pigs. The BBD was introduced to the CMs using an ionic gelation process involving tripolyphosphate (TPP). Colostrum-deprived pigs were then directly immunized through intranasal administration of the BBD-CMs. A challenge with a field isolate of B. bronchiseptica was performed ten days following the final immunization. The BBD-specific IgG and IgA titers, evident in the nasal wash and serum from the vaccinated pigs, increased with time (p<0.05). Following the challenge, the clinical signs of infection were about 6-fold lower in the vaccinated pigs compared with the nonvaccinated pigs. The grades for gross morphological changes in the turbinate bones from the vaccinated pigs were also significantly lower than the grades recorded for the nonvaccinated pigs (p<0.001). Therefore, the mucosal and systemic immune responses induced in the current study would seem to indicate that the intranasal administration of BBD-CMs may be an effective vaccine against atrophic rhinitis in pigs.

Staphylococcus aureus enterotoxin B, protein A, and lipoteichoic acid stimulations in nasal polyps.

BACKGROUND: Increasing evidence points toward a modifying role of Staphylococcus aureus and its products in the pathogenesis of nasal polyposis. OBJECTIVE: The aim of this study was to investigate cytokine and mediator production after stimulation with S aureus-derived proteins enterotoxin B, protein A, and lipoteichoic acid in nasal polyp and control inferior turbinate tissue. METHODS: Tissue fragments were stimulated with RPMI (negative control), enterotoxin B, protein A, and lipoteichoic acid for 30 minutes and 24 hours. Supernatants were measured by multiplex for proinflammatory cytokines (IL-1beta, TNF-alpha) and T-cell and subset-related cytokines (IFN-gamma, IL-2, IL-4, IL-5, IL-8, IL-10, IL-12p70, IL-13). Histamine, TGF-beta1, cysteinyl leukotrienes, and prostaglandin D(2) were analyzed by ELISA. RESULTS: Thirty minutes of protein A stimulation resulted in a significant increase of histamine, leukotrienes, and prostaglandin D(2). Enterotoxin B stimulation over a period of 24 hours induced a significant increase of IL-1beta, TNF-alpha, IFN-gamma, IL-2, IL-4, IL-5, IL-10, and IL-13 in both groups, with this increase significantly higher in nasal polyps compared with controls. CONCLUSION: We here show that S aureus products have various effects on mucosal tissues: surface protein A induces mast cell degranulation, whereas enterotoxins induce the release of cytokines, with a T(H)2-skewed pattern in nasal polyps, supporting the stimulatory role of superantigens in the development of this inflammatory disease.

Submucous turbinectomy combined with posterior nasal neurectomy in the management of severe allergic rhinitis: clinical outcomes and local cytokine changes.

OBJECTIVES: Submucous resection of the inferior turbinate is one of the recommended methods to alleviate nasal symptoms in patients with severe allergic rhinitis patients in terms of postoperative results and preservation of nasal function. Posterior nasal neurectomy, recently developed by Kikawada, is a novel method to selectively cut the neural bundles out from the sphenopalatine foramen and to diminish the complaints of hypersecretion. This study was carried to examine the clinical effectiveness and changes in local cytokine levels of this combined surgical procedure. METHODS: Twenty-three patients with severe perennial allergic rhinitis underwent submucous turbinectomy combined with posterior nasal neurectomy under general anesthesia. The patients' subjective nasal symptoms were examined at each visit. The levels of interleukin-5 (IL-5), eotaxin and regulated on activation, normal T cell expressed and secreted (RANTES) in nasal lavages were measured before and 6 month after surgery. Nasal mucosa of the inferior turbinate was also obtained for histopathological examination in some cases. RESULTS: The mean symptom scores for sneeze, rhinorrhea, nasal obstruction, and total severity were all statistically decreased after surgery. Therapeutic effects continued to be apparent as long as 3 years after surgery. The mean levels of both IL-5 and eotaxin significantly decreased after surgery, but that of RANTES remained unchanged. Histopathological examination revealed that the number of inflammatory cells and nasal glands markedly reduced in lamina propria and the epithelial layer became covered with stratified columnar cells. CONCLUSION: Submucosal turbinectomy with posterior nasal neurectomy has remarkably improved subjective nasal symptoms in patients with severe allergic rhinitis on a long-term follow-up basis. The present study also demonstrates that the clinical effectiveness of the procedure is accompanied by decreases in local inflammatory cell infiltration and the related cytokine production.