Differential protein expression in the secretory fluids of maxillary sinusitis and maxillary retention cyst.

Both maxillary sinusitis (MS) and maxillary retention cyst (MRC) involve the maxillary sinus and show similar clinical features. Clinically, differentiating between MS and MRC is sometimes difficult in asymptomatic patients, despite their quite different pathogenic behaviors. To identify differential protein expressions in the secretory fluids of MS and MRC, 25 cases of asymptomatic MS and 15 cases of asymptomatic MRC were examined pathologically in this study. All patients underwent routine endoscopic sinus surgery or modified Caldwell-Luc procedure and the sinus mucosal specimens obtained during these procedures with the approval of the Institutional Review Board. Their secretory fluids were analyzed via immunoprecipitation-based high-performance liquid chromatography (IP-HPLC) using 25 types of antiserum, including inflammatory cytokines, antimicrobial proteins, and mucosal protective proteins. In the histological examinations, MS and MRC showed similar features in the secretory columnar epithelial lining and thick submucosal connective tissue, both of which contained few inflammatory cells infiltrates. The IP-HPLC analysis revealed that TNFα, IL-1, -8, MMP-3, -10, α1-antitrypsin, cathepsin C, lysozyme, lactoferrin, ß-defensin-1, -3, LL-37, mucocidin, and mucin-1 were more intensely expressed in MS than in MRC; whereas IgA, cystatin A, and proline-rich proteins were more strongly expressed in MRC than in MS. These data indicate that the secretory fluid of MS is indicative of a more robust inflammatory reaction to certain bacteria compared to that of MRC, while the secretory fluid of MRC contains more abundant mucosal protective proteins compared to that of MS. Taken together, the IP-HPLC analysis of MS and MRC secretory fluid revealed that MRC showed a weaker inflammatory reaction but a stronger mucosal protective function than MS.

Enhanced podoplanin expression in chronic maxillary sinusitis.

Podoplanin expression has been reported in oral squamous epithelium, myoepithelia of the salivary glands, and odontogenic lesions, and has been linked with inflammatory and neoplastic conditions. We hypothesized that inflamed respiratory mucosa of the maxillary sinus also express podoplanin, especially in cases with odontogenic sinusitis. We retrospectively investigated podoplanin expression in biopsies from maxillary sinus with inflammatory changes. Cases with chronic rhinosinusitis with polyp formation (n=5), chronic rhinosinusitis without polyps (n=5), chronic rhinosinusitis with eosinophilia (n=5), and odontogenic chronic rhinosinusitis (n=5) were investigated immunohistochemically using an established antibody for podoplanin (D2-40). Respiratory epithelium in chronic maxillary sinusitis with polyp formation did not exhibit enhanced podoplanin expression. However, D2-40 positivity was detected in the basal cells in all cases with chronic sinusitis associated with inflammatory infiltrations as well as in the parabasal epithelial layer in chronic sinusitis without polyp formation. We observed podoplanin expression in non-neoplastic maxillary sinus epithelium exhibiting inflammatory changes. We suggest that podoplanin is involved in the pathogenesis of chronic rhinosinusitis, particularly in the intraepithelial migration of inflammatory infiltrates.

Does the maxillary sinus have a triggering role in nasal nitric oxide synthesis?

OBJECTIVES: We investigated whether the maxillary sinus plays a stimulatory role in nasal nitric oxide (NO) synthesis. Research on sinusitis and nasal polyps has found low NO levels in exhaled air and linked this to obstruction of the ostium. However, the major source of NO in exhaled air is thought to be the nasal mucosa. In this study, Streptococcus pneumoniae was applied to the maxillary sinus to investigate changes in NO synthesis of the nasal mucosa. METHODS: An experimental study was performed with New Zealand white rabbits. Three groups, pneumococcus, control and sham, were created. The maxillary sinus of the pneumococcal group was exposed to Streptococcus pneumoniae suspension. Before and after the exposure, bilateral biopsy specimens were taken from the inferior turbinate. Specimens were examined by RT-PCR for expressions of endothelial nitric oxide synthase (e-NOS) and inducible nitric oxide synthase (i-NOS). Physiological saline solution was administered to the maxillary sinus in the control group and biopsies were obtained. The sham group underwent only biopsy. RESULTS: A significant increase in i-NOS expression of tissue samples from the pneumococcal group on the same and opposite sides were detected. There was no increase in e-NOS expression in this group. The control and sham groups had no significant change in i-NOS or e-NOS expression. CONCLUSION: In the acute period after the maxillary sinus is exposed to a pathogen, i-NOS expression increases in the nasal mucosa, but endothelial NOS expression is not affected. Consequently, a combined response in the maxillary sinus and the nasal mucosa for nitric oxide synthesis is shown in the present study.

Evidence of maxillary sinus inflammation in seasonal allergic rhinitis.

OBJECTIVE: Allergic rhinitis has been frequently associated with both acute and chronic sinusitis. Previous studies have shown an influx of eosinophils into the maxillary sinus after nasal challenge with allergen. The objective of this study was to determine, in humans, if the development of seasonal allergic inflammation, secondary to natural allergen exposure, leads to similar inflammation within the maxillary sinus. STUDY DESIGN: Prospective, longitudinal study. Setting. Academic medical center and research laboratory. SUBJECTS AND METHODS: Eighteen subjects were evaluated in and out of the ragweed allergy season using subjective measures (nasal symptoms, quality of life), nasal secretory response to methacholine challenge, and evaluation of biomarkers in nasal and sinus lavages. RESULTS: The subjects became symptomatic during the season and reported worse quality of life and increased nasal reactivity to methacholine. The total number of eosinophils obtained by nasal lavage during the season (median= 35,691) was significantly higher compared with out of season (median = 2811, P ≤ .02). Similarly, there were significantly more eosinophils, albeit to a lesser magnitude, in the maxillary sinus during the season (median = 4248) compared with the out-of-season samples (median = 370, P ≤ .02). CONCLUSION: The authors provide evidence that natural exposure to pollen during an individual's allergy season leads to both nasal and sinus inflammation, strengthening the association between allergic rhinitis and sinusitis. The mechanism of this inflammatory response needs to be elucidated.

Mucosal eosinophils and l-selectin ligands are associated with invasive and noninvasive sinus surgery outcomes.

BACKGROUND: Chronic rhinosinusitis (CRS) is characterized by persistent inflammation of the nasal and paranasal mucosa with numerous emigrated leukocytes. L-Selectin on leukocytes and its endothelial glycosylated ligands initiate leukocyte infiltration into inflamed tissues. Endoscopic sinus surgery (ESS) is the major approach for restoring sinus physiology after failure of conservative therapy; however, the effect of enlarging the maxillary sinus ostium is still unknown. Here, we compared two histological markers of local inflammation, the number of mucosal eosinophils, and the expression of endothelial L-selectin ligands, with clinical outcomes after enlarging or saving the maxillary sinus ostium. METHODS: Twenty-three patients with CRS underwent uncinectomy on one side and additional middle meatal antrostomy on the other side. Maxillary sinus mucosa biopsy specimens from these patients and nine healthy subjects were taken for immunohistochemical evaluations of the number of mucosal eosinophils and endothelial L-Selectin ligands. Also, symptoms and mucociliary clearance were measured. RESULTS: The postoperative reduction of the endothelial L-Selectin ligands was independent of the operation technique. There was a correlation between postoperative number of mucosal eosinophils and symptom score, which was also independent of the surgical technique. The postoperative decrease of mucosal eosinophils, as well as the correlation of the intraoperative eosinophils with the postoperative symptom score, was found only on antrostomy side. CONCLUSION: ESS decreases the expression of endothelial L-Selectin ligands, which might lead to decreased eosinophil traffic into maxillary sinus mucosa, putatively more when enlarging the maxillary sinus ostium. Both intra- and postoperative low number of eosinophils seem to be indicators of good subjective recovery.

The effects of methylprednisolone and cefazolin sodium on antioxidant status in experimentally induced maxillary sinusitis.

CONCLUSION: Sinusitis is accompanied by deteriorated antioxidant status, which can be alleviated with administration of cefazolin sodium or methylprednisolone. Steroids improve sinusitis when combined with antibiotics. OBJECTIVE: To evaluate the antioxidant status in response to treatment of maxillary sinusitis with methylprednisolone and cefazolin sodium. MATERIALS AND METHODS: Twenty-eight rabbits were inoculated with Staphylococcus aureus and then treated with saline, methylprednisolone, cefazolin sodium, and methylprednisolone plus cefazolin sodium, twice daily for 7 days. After the animals were sacrificed, mucosa samples were obtained to determine catalase (CAT), superoxide dismutase (SOD), and glutathione reductase (GPx) activities and levels of nitric oxide (NO) and malondialdehyde (MDA). RESULTS: Catalase activity among untreated rabbits and those treated with either methylprednisolone or cefazolin sodium was not different. Activities of SOD and GPx were lower for rabbits treated with cefazolin sodium than for those treated with methylprednisolone and for untreated rabbits (p<0.0001). Rabbits treated with cefazolin sodium had lower NO and MDA levels than those treated with methylprednisolone and untreated rabbits (p<0.0001). Combined administration of cefazolin sodium with methylprednisolone increased CAT, SOD, and GPx activities further and decreased NO and MDA levels further in comparison with their administration alone (p<0.0001).

Differential deposition of aerosols in the maxillary sinus of human cadavers by particle size.

BACKGROUND: Topical delivery of nebulized antibiotics to the paranasal sinuses has been shown to improve clinical outcomes in patients with chronic sinus disease after functional endoscopic sinus surgery (FESS). The most efficient method for delivering nebulized particles to the sinuses, however, has not been established. This study investigates how the size of nebulized particles influences the efficiency of deposition in the maxillary sinus of human cadavers after FESS. METHODS: Endoscopic maxillary antrostomy was performed on eight sides in four cadavers. Each cadaver's nasal vault was nebulized with technetium99m-labeled sulfur colloid particles of three size ranges. Anterior-posterior and left lateral static gamma-camera images of the head were captured with an acquisition cutoff limit of 30,000 gamma-count. Regions of interest were defined for the left and right maxillary sinus and gamma-photon counts were recorded. Analysis of variance (ANOVA) for repeated measures and paired t-test were used to determine statistical significance. RESULTS: Mean diameter of particles generated was 6, 0.99, and 0.67 microm. There was a statistically significant difference in deposition between the largest particle size and the two smaller sizes, with a mean gamma-photon count of 254 for 6-microm particles versus 811 for 0.99-microm particles and 835 for 0.67-microm particles (ANOVA, p = 0.002). CONCLUSION: Particles in the 0.67- to 0.99-microm range had improved efficiency of deposition in the maxillary sinus compared with larger particles after maxillary antrostomy. Larger particles appeared to deposit directly in the nasal vault while smaller particles were more likely to reach the maxillary sinus.

Experimentally induced acute sinusitis and efficacy of vitamin A.

CONCLUSIONS: Although antibiotics are the mainstays for treatment of sinusitis, they do not specifically treat tissue damage due to free radicals. We propose that antioxidant, anti-infective, immunomodulator vitamin A may be a useful addition in the management of sinusitis. OBJECTIVES: Acute sinusitis is one of the most common diseases in humans. Vitamin A is a fat-soluble vitamin and essential for immunity, cellular differentiation, and maintenance of respiratory and gastrointestinal epithelial surfaces, growth, reproduction, and vision. The objective of this study was to investigate the therapeutic role of vitamin A on healing of acute sinusitis. MATERIALS AND METHODS: This was a prospective controlled animal trial. Experimental sinusitis was induced by blocking the right nose and inoculating Streptococcus pneumoniae into the right maxillary sinuses. Left maxillary sinuses were used as controls. Rabbits were divided in to two groups. At 48 h after inoculation, group I received only parenteral ampicillin-sulbactam (50 mg/kg), group II was treated with parenteral ampicillin-sulbactam (50 mg/kg) and parenteral a dose of 100,000 IU vitamin A in palmitate form. All animals were sacrificed on the 10th day. Mucosal samples were excised from the infected and control sinuses for histopathologic examination, for measurement of activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT), and for evaluation of levels of malondialdehyde (MDA) and nitric oxide (NO). RESULTS: All the infected sinuses displayed signs of inflammation, but there was no statistically significant difference between the study and control groups. In our study, epithelial integrity as well as NO and MDA levels were better in the group receiving both antibiotic and vitamin A than the group receiving antibiotic alone. Nevertheless, SOD activity was significantly increased in the group receiving only antibiotics, compared with the control mucosal SOD activity. There was no difference between the groups as regards CAT and GSH activity.

[Diffusion of methylene blue in the human maxillary sinus mucosa].

The coefficient of diffusion of methylene blue in pathologically changed human maxillary sinus mucosa in vitro has been estimated for the first time. The mean value of the diffusion coefficient is (4.8 +/- 2.9) x 10(-7) cm2/s. The method is based on the registration of the dynamics of reflectance of tissue samples under the action of the dye. The diffusion coefficient has been estimated by approximation of experimental data in the framework of the model presented.

Unusual recurrence in ureters and maxillary sinus of Langerhans cell histiocytosis involving mastoid bone.

We present a case of Langerhans cell histiocytosis (LCH) diagnosed in the mastoid bone. The tumor recurred in the ureter and maxillary sinus mucosa two years later. The diagnosis of LCH was based on morphology and immunohistochemistry. Involvement of the ureter and the maxillary sinus in LCH is extremely rare. To the best of our knowledge, this is the first case of LCH affecting the mastoid bone in a 16-year-old boy and recurring later in the ureter and maxillary sinus mucosa.

Endothelial L-selectin ligands in sinus mucosa during chronic maxillary rhinosinusitis.

RATIONALE: Chronic rhinosinusitis is characterized by persistent inflammation of the nasal and paranasal mucosa with numerous emigrated leukocytes. L-selectin on leukocytes and its endothelial glycosylated ligands initiate organ-specific leukocyte infiltration into inflamed tissues. OBJECTIVES: The purpose of this study was to evaluate the endothelial expression of functionally active endothelial L-selectin ligands, sulfated sialyl Lewis x, in maxillary sinus mucosa from patients with chronic rhinosinusitis and from normal control subjects. METHODS: Maxillary sinus mucosa specimens (116) were obtained surgically and immunohistochemically stained with monoclonal antibodies detecting sialyl Lewis x or sulfated extended core 1 lactosamines. The severity of the inflammation was determined by intraoperative endoscopic findings, computed tomography scans, and histopathologic assessment of the specimens. MEASUREMENTS AND MAIN RESULTS: The percentage of vessels expressing endothelial sulfated sialyl Lewis x epitopes increased during chronic rhinosinusitis compared with uninflamed control tissue, especially in patients with additional allergic rhinitis, and decreased in specimens from aspirin-intolerant patients with preoperative oral corticosteroid treatment. In addition, the expression level of endothelial sulfated sialyl Lewis x epitopes and the number of mucosal eosinophils correlated with the severity of the inflammation, and decreased in specimens taken 9 months postoperatively compared with intraoperative samples, especially in patients with intranasal corticosteroid treatment. CONCLUSIONS: Our results suggest that functionally active L-selectin ligands might guide leukocyte traffic into maxillary sinus mucosa preferentially in patients with severe findings of chronic maxillary rhinosinusitis, thus leading to aggravation of the inflammation.

Serum and mucosal nitric oxide levels and efficacy of sodium nitroprussid in experimentally induced acute sinusitis.

Experimental acute sinusitis was induced in 21 New Zealand hybrid rabbits by occluding the ostium and inoculating them with Streptococcus pneumonia. While a group of rabbits with sinusitis was left untreated, two other groups were administered parenteral sodium nitroprussid (SNP) and oral levofloxacin for ten days. While staphylococci species, non-hemolytic streptococcus and contaminated flora were isolated from the sinuses of controls, Streptococcus pneumonia was re-isolated in two of six untreated rabbits, in one of six SNP administered rabbits and none of the levofloxacin treated rabbits. Serum and maxillary sinus mucosal nitric oxide (NO) levels were correlated. While the mean maxillary sinus NO level of controls was significantly higher than that of untreated rabbits, the mean maxillary sinus and serum NO levels were significantly higher in SNP administered rabbits than in the others. Although goblet cell hyperplasia and squamous cell metaplasia were detected in some slides, edema and neutrophil infiltration were the prominent findings. The most severe inflammatory changes were found in the untreated sinusitis group on the third and fifth days. The earliest improvement was observed in the levofloxacin treated rabbits. It was concluded that NO level is decreased during acute sinusitis and that SNP administration hastens the bacteriological and histological recovery.

Hypoxia in paranasal sinuses of patients with chronic sinusitis with or without the complication of nasal allergy.

OBJECTIVE: In order to elucidate the pathogenesis of the radiologic opacity of the sinuses frequently observed in patients with allergic rhinitis, the mechanisms underlying their sinus mucosal swelling were studied clinically. MATERIAL AND METHODS: We confirmed the presence of hypoxia in inflamed sinuses and obstruction of the sinus ostium in operated patients with chronic sinusitis by digitally monitoring the oxygen tension. The possibility of radiologic sinus shadow was also investigated after transient obstruction of the natural ostium. RESULTS: The oxygen tension was significantly lower in inflamed than non-inflamed sinuses (p < 0.01), irrespective of the presence or absence of allergic rhinitis. In 54.5% of patients without sinusitis, transient obstruction of the middle meatus by gauze packing resulted in the appearance of a pathologic sinus shadow on radiograms obtained after septoplasty and turbinotomy. In both allergic and non-allergic rhinitis, thick opacity was the most frequently encountered pattern (p < 0.01). CONCLUSION: Our study revealed that in the absence of a primary allergic reaction in the sinus mucosa, blocking of the middle meatus and ostium by allergic swelling of the nasal mucosa may induce hypoxia and secondary mucosal swelling in the sinuses.

Lipid peroxidation and antioxidant enzyme activities in experimental maxillary sinusitis.

The aims of this study were to assess whether th e increased oxidative stress of acute maxillary sinusitis is reflected by tissue lipid peroxidation and whether the activities of selected antioxidant enzymes are altered during inflammation of the maxillary sinus mucosa. Unilateral rhinosinusitis was induced in 8 rabbits by instillation of 0.2 ml of a killed suspension of Staphylococcus aureus into the right maxillary sinus cavity; control instillation of saline solution into the left maxillary sinus cavity of the same rabbits was also performed. At 7 days post-treatment, mucosal samples were excised from the treated and control sinuses for measurements of superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) and malondialdehyde (MDA). The SOD activity in mucosa of the inflammed sinuses was significantly higher than in control sinus mucosa; GPx activity was significantly lower in the inflammed sinuses than in the controls. No significant differences were found in CAT activities or MDA levels of the inflammed versus the control sinus mucosa. These findings demonstrate that experimental induction of acute maxillary sinusitis in rabbits does not increase lipid peroxidation as evidenced by MDA levels in the sinus mucosa, but does alter the activities of some antioxidant enzymes.

Anti-inflammatory activity of clarithromycin in adults with chronically inflamed sinus mucosa.

In a phase IV, open-label study, 25 patients with clinically stable chronic sinusitis and persistent maxillary sinus inflammation were treated for 14 days with clarithromycin 500 mg twice daily. Biopsy specimens of the maxillary sinus mucosa were obtained pretreatment and evaluated for macrophages (CD68), eosinophils (MBP), elastase, interleukin-6 (IL-6), IL-8, tumor necrosis factor-alpha (TNF-alpha), and activity of eosinophils (EG2), as well as edema score. Clinical signs and symptoms were assessed pretreatment, at the end of treatment, and 1 and 2 weeks later. Statistically significant reductions (P < or = .05) from pretreatment were observed for all markers of sinus mucosal inflammation, including CD68, EG2, elastase, IL-6, IL-8, TNF-alpha, and edema score, with a trend to decreased total eosinophil count. Improvement was observed for all clinical signs and symptoms of chronic sinusitis--sinus pain, sinus headache, nasal congestion, nasal discharge, and mucopurulent discharge--up to 14 days after the end of treatment. Cultures to evaluate persistent infection with Chlamydia pneumoniae showed negative results. Significant reductions in various markers of sinus mucosal inflammation support the role of clarithromycin in modulating immunologic responses. Improvement of clinical signs and symptoms in patients with chronic inflammatory sinusitis not meeting criteria for known or presumed bacterial infection was also noted up to 2 weeks after completion of a 14-day course of clarithromycin.

Production of beta-defensin antimicrobial peptides by maxillary sinus mucosa.

beta-Defensins are endogenous cationic peptides with broad-spectrum antimicrobial activity that are thought to play a role in the innate immune response. Two human beta-defensins, beta-defensin-1 (HBD-1) and beta-defensin-2 (HBD-2), have been identified. These peptides have recently been characterized in several human tissues. The presence of these peptides in the paranasal sinuses has not been investigated. We examined maxillaary sinus secretions from six patients with sinusitis and 10 patients without signs, symptoms, or radiologic evidence of sinus disease for the presence of beta-defensins. Cationic peptides were extracted from antral lavage specimens and examined for the presence of HBD-1 and HBD-2 by Western blot. Normal maxillary sinus epithelium was obtained from two patients and analyzed by RT-PCR for the presence of HBD-1 and HBD-2 mRNA. Tissue immunostaining for the two peptides was also used. Western blot analysis identified HBD-1 in two of 10 patients in the control group and in three of six patients in the sinusitis group. HBD-2 was identified in one of 10 patients in the control group and in four of six patients in the sinusitis group. RT-PCR revealed HBD-1 mRNA in one of two normal controls tested. Immunostaining localized HBD-1 and HBD-2 to the epithelial cell cytoplasm. This is the first demonstration of HBD-1 and HBD-2 production in the paranasal sinuses. In the present study, HBD-1 and HBD-2 were detected more frequently in the maxillary sinus fluid of patients with inflamed sinuses than in normal controls.

Eosinophilic apoptosis in sinus mucosa: relationship to tissue eosinophilia and its resolution in allergic sinusitis.

BACKGROUND: Apoptosis, which is regulated by both cell survival and death signals, is important for the swift clearance of unwanted cells. OBJECTIVE: We sought to elucidate whether eosinophilic apoptosis is associated with tissue eosinophilia and to determine its resolution in allergic sinusitis (AS). METHODS: Numbers of eosinophils, numbers of IL-5(+) cells, and the apoptosis index of eosinophils were calculated in the submucosa (both superficial and deep layers) of patients with AS by using histochemical methods before and after prednisolone treatment. Patients without AS were used for control groups. Anti-EG2 antibody was used to identify eosinophils. IL-5, Fas, or Bax expression of eosinophils was evaluated to elucidate the role of the factors affecting eosinophilic apoptosis. RESULTS: EG2 and IL-5(+) cells were abundant in the submucosa of patients with AS, especially in the superficial layer. About 50% to 60% of the IL-5-producing cells were eosinophils. Apoptotic eosinophils were less numerous in the superficial layer than the deep layer in these diseases. After prednisolone treatment, an induction of eosinophilic apoptosis was accompanied by a significant decrease in the number of EG2(+) and IL-5(+) cells. No remarkable difference was observed in the Fas or Bax expression of eosinophils after prednisolone treatment. CONCLUSION: Autocrine secretion of IL-5 from eosinophils may be one reason why eosinophilic disease is difficult to manage. Induction of eosinophilic apoptosis is critical for reversing tissue eosinophilia in patients with AS.

Interferon gamma levels in the sinus, ear, and airway in a rabbit sinusitis model induced by Bacteroides inoculation.

BACKGROUND: Previously, we found minimal bacterial dissemination and no evidence of systemic inflammation in a rabbit sinusitis model in which the left maxillary sinus was inflamed by Bacteroides inoculation with the ostium closed. However, we observed an increase in anti-Bacteroides IgG antibodies in the contralateral sinus, lower airway, and middle ear, with an apparent increase in interferon gamma (IFN-gamma) messenger RNA expression in the ear and sinus mucosa. OBJECTIVE: To evaluate how IFN-gamma production in the upper and lower airway is associated with localized bacterial sinusitis. DESIGN: Interferon gamma levels were measured in lavage solutions from the sinus, airway, and middle ear and in serum at 1, 2, 3, and 4 weeks following bacterial inoculation. SUBJECTS: The subjects were 6 rabbits at each time point. The controls were untreated (n = 5) and sham-operated (n = 4-5) rabbits at 2 and 4 weeks. INTERVENTION: Bacteroides fragilis (10(8) plaque-forming units) was inoculated into the left maxillary sinus. RESULTS: Interferon gamma levels in the ear and sinus were less than 0.2 microg/g protein in controls. Following bacterial inoculation into the left sinus, IFN-gamma levels increased up to 10-fold in both sinuses and even more in the middle ear at 3 weeks, independent of bacterial dissemination. Mean +/- SD IFN-gamma levels in the airway (0.3+/-0.28 microg/g protein in controls) were not altered by bacterial inoculation into the sinus. Serum IFN-gamma levels were very low (<0.05 microg/g protein) in most rabbits and were unchanged by bacterial inoculation. CONCLUSIONS: Interferon gamma levels increase in the ear and contralateral sinus in response to localized sinus inflammation, indicating concerted mucosal proinflammatory immune responses in the upper airway. Such responses may lead to the aseptic middle ear inflammation often observed in patients with chronic sinusitis.

Immunohistochemical localization of cytokines and cell adhesion molecules in maxillary sinus mucosa in chronic sinusitis.

OBJECTIVE: Chronic sinusitis is a common disease characterized by persistent inflammation of the nasal and paranasal sinus mucosa. Accumulating evidence supports the importance of proinflammatory cytokines and endothelial cell adhesion molecule (CAM) expression as an initiating process in tissue inflammation. This study was conducted to investigate the localization of major cytokines and CAMs in the maxillary sinus mucosa from patients with chronic sinusitis and from normal subjects. METHODS: Maxillary sinus mucosal specimens from patients with chronic sinusitis (n = 10) and from normal subjects (n = 6) were immunostained with specific antibodies directed against the cytokines (IL-1alpha, IL-1beta, IL-6, IL-8 and TNF-alpha) and the CAMs (intercellular adhesion molecule-1, ICAM-1 and vascular CAM-1, VCAM-1). RESULTS: The number of immunoreactive cells for IL-1alpha, IL-1beta, IL-6, IL-8, and TNF-alpha was increased significantly in patients with chronic sinusitis compared with normal controls. Immunoreactivity for ICAM-1 was also increased significantly in patients with chronic sinusitis compared with normal controls, whereas VCAM-1 is only minimally expressed or is absent in both groups. CONCLUSION: These findings indicate that bacterial and/or viral infection may induce functional and morphologic changes in the maxillary sinus mucosa in chronic sinusitis through enhanced generation of specific cytokines in conjunction with CAMs.

Comparison of inflammatory cell profile and Th2 cytokine expression in the ethmoid sinuses, maxillary sinuses, and turbinates of atopic subjects with chronic sinusitis.

Chronic sinusitis is a common disease characterized by persistent inflammation of the sinus mucosa. This study was undertaken to investigate immunopathologic findings in biopsy specimens from the ethmoid sinuses, maxillary sinuses, and inferior nasal turbinates of 14 allergic subjects with chronic sinusitis. The composition of the inflammatory infiltrate in the three tissue sites was examined by immunocytochemistry with anti-CD3 (total T cells), anti-CD4 (helper T cells), anti-CD8 (suppressor T cells), anti-MBP (eosinophils), antitryptase (mast cells), and antichymase (mast cells) antibodies. These revealed a significant increase in the T-cell helper/suppressor ratio and eosinophils in the ethmoid sinus mucosa compared with those in the maxillary sinus mucosa and the inferior turbinate. Eosinophil numbers were also higher in the maxillary sinus than in the inferior turbinate. Mast cells were present in significantly higher numbers in the ethmoid sinus and inferior turbinate biopsy sections than in the maxillary sinus. With antisense, radiolabeled riboprobes, we used in situ hybridization to examine the expression of interleukin-4 and interleukin-5 transcripts. The density of cells expressing interleukin-4 transcripts was significantly higher in the inferior turbinate biopsy sections than in those from the ethmoid and maxillary sinuses. In addition, the number of interleukin-4 mRNA-positive cells was higher in the ethmoid than in the maxillary sinus mucosa. The density of interleukin-5 mRNA-positive cells was significantly higher in the ethmoid and maxillary sinuses than in the inferior turbinate. The results of this study indicate (1) a more intense inflammatory response in the ethmoid sinus than in the maxillary sinus and inferior turbinate in allergic chronic sinusitis and (2) different inflammatory responses in the upper airways that are dependent on the anatomic site. These findings have potential implications in the design of new therapeutic interventions for allergic chronic sinusitis.