Martin Wagenmann

IL-5 synthesis is upregulated in human nasal polyp tissue

BACKGROUND In most nasal polyps, tissue eosinophilia is a striking finding, the pathologic mechanism of which is not understood. OBJECTIVE This study was performed to investigate a possibly distinct cytokine and chemokine pattern that could explain the characteristic tissue eosinophilia in nasal polyps. METHODS Polyps from 23 patients and turbinate tissue from 18 control subjects were investigated. The cytokine protein content (IL-1 beta, IL-3, IL-4, IL-5, IL-6, IL-8, IL-10, tumor necrosis factor-alpha, granulocyte-macrophage colony-stimulating factor, IL-1RA, RANTES, GRO-alpha) of tissue homogenates was measured by ELISA. Immunohistochemistry was performed in selected samples to detect IL-5+, major basic protein-positive, and EG2+ cells. RESULTS IL-5 was detectable in only one sample of tissue from 18 control subjects but was found in 18 of 23 nasal polyps. Immunohistochemistry revealed an abundant number of IL-5+ cells, of which 69.5% could be identified as eosinophils by morphology. IL-6, IL-8, IL-10, tumor necrosis factor-alpha, GRO-alpha, and RANTES were detected in all specimens, without significant differences between groups (p > or = 0.05), whereas significnatly higher concentrations of IL-1 beta and IL-1RA were found in turbinate mucosa (p < or = 0.05). IL-3 was not detectable: granulocyte-macrophage colony-stimulating factor could only occasionally be found. CONCLUSION This study indicates that IL-5 plays a key role in the pathophysiology of eosinophilic nasal polyps and may be produced by eosinophils.

Proinflammatory Cytokines: Measurement in Nasal Secretion and Induction of Adhesion Receptor Expression

We recently demonstrated that interleukin (IL)-1 beta, tumor necrosis factor (TNF)-alpha, IL-6 and IL-8 can be found in nasal secretions from allergic rhinitis patients under artificial and natural conditions. By ELISA measurements, significantly elevated baseline levels for IL-1 beta, IL-6 and IL-8 were found in seasonal allergic compared to control subjects. Within the first 2 h after nasal allergen challenge, IL-1 beta and TNF are secreted, whereas IL-6 and IL-8 showed a slow increase over 6-8 h. All cytokine levels returned to baseline within 24 h after exposure. Repeated measurements at 4-week intervals in perennial allergic rhinitis subjects (n = 27) showed significant correlations between IL-1 and IL-8, IL-6 and IL-8 and IL-6 and the symptom score (visual analogue scale). The IL-1 receptor antagonist IL-1ra was found in great molar excess in the secretions and correlated significantly with IL-8, but not IL-1 beta. In an in vitro assay using fresh nasal mucosa of grass-pollen-allergic subjects, we were able to demonstrate a strong and rapid induction of E-selectin adhesion receptor expression on endothelial cells by allergen, IL-1 beta and TNF. The adhesion receptor expression was markedly inhibited by soluble IL-1 receptors, sTNF-R and IL-1ra. These data indicate a key role for inflammatory cytokines in the regulation of allergic inflammation.

Anatomic and physiologic considerations in sinusitis

The anatomy and physiology of the nose, the paranasal sinuses, and related structures are of major importance in understanding sinusitis. A brief description of the airflow, blood flow, nasal cycle, histology and the developmental anatomy are given. These elements combine to condition inhaled air by warming, humidifying, and filtering it. An important mechanism for understanding sinusitis is mucociliary clearance. The nasal cavity and the paranasal sinuses are covered by a pseudostratified, columnar, ciliated epithelium with a thin mucous layer on top of it. In the sinuses the beat of the cilia is directed toward their natural ostia. The ostia of most of the paranasal sinuses lead into the region of the middle meatus and the anterior ethmoid, the osteomeatal complex. Obstruction in this area reduces clearance and plays a major role in the pathophysiology of sinusitis.

Elevated levels of interleukins IL-1β, IL-6 and IL-8 in naturally acquired viral rhinitis

We studied the cytokines IL(interleukin)-1β, IL-4, IL-6 and IL-8 in nasal lavage samples from 20 patients with naturally acquired viral rhinitis and 5 healthy controls without nasal complaints. IL-1β, IL-6 and IL-8 levels in lavage fluid from the viral rhinitis patients were significantly elevated when compared to control subjects. IL-4 was not measurable in any of the samples. The cytokine levels in secretions from the healthy controls remained stable intraindividually on 5 consecutive sampling days. We suggest that cytokines such as IL-1β, IL-6 and IL-8, but not IL-4, are involved in the pathophysiology of the common cold.

Complications of sinusitis

Even though they seldomly occur, the complications of sinusitis may be life-threatening. Complications can be local, orbital, and intracranial problems or combinations thereof. Orbital complications are the most frequent, and children with acute ethmoiditis are especially prone to them. To prevent permanent loss of vision, immediate and intense therapy is most important. Intracranial complications can have few symptoms, and discordance between symptoms and severity is not uncommon, which involves the importance of early radiologic diagnosis with computed tomographic or magnetic resonance imaging scans. Orbital and intracranial complications of sinusitis are medical emergencies and must be treated by specialists. Whenever possible, the underlying sinus infection should be drained at the same time. All physicians treating acute and chronic sinusitis must keep the potentially life-threatening complications of sinusitis in mind and remain suspicious because early recognition and treatment are crucial in these cases.

The time course of the bilateral release of cytokines and mediators after unilateral nasal allergen challenge.

Background:  Late phase reactions after allergen challenge can be understood as a correlate of the inflammatory reaction in allergic rhinitis.

Guidelines on the management of IgE-mediated food allergies

S2k-Guidelines of the German Society for Allergology and Clinical Immunology (DGAKI) in collaboration with the German Medical Association of Allergologists (AeDA), the German Professional Association of Pediatricians (BVKJ), the German Allergy and Asthma Association (DAAB), German Dermatological Society (DDG), the German Society for Nutrition (DGE), the German Society for Gastroenterology, Digestive and Metabolic Diseases (DGVS), the German Society for Oto-Rhino-Laryngology, Head and Neck Surgery, the German Society for Pediatric and Adolescent Medicine (DGKJ), the German Society for Pediatric Allergology and Environmental Medicine (GPA), the German Society for Pneumology (DGP), the German Society for Pediatric Gastroenterology and Nutrition (GPGE), German Contact Allergy Group (DKG), the Austrian Society for Allergology and Immunology (OGAI), German Professional Association of Nutritional Sciences (VDOE) and the Association of the Scienti‰c Medical Societies Germany (AWMF)

The effect of terfenadine on unilateral nasal challenge with allergen

To investigate the role of H1 receptor-mediated effects in allergic rhinitis, we challenged 12 allergic volunteers with allergen 2 hours after administration of either placebo or 60 mg of terfenadine. Filter paper discs were used for the unilateral administration of allergen and the collection of nasal secretions. Secretion weights, levels of histamine in recovered nasal secretions, and nasal airway resistance (NAR) were measured for each nostril separately, and the number of sneezes was counted. After placebo treatment, allergen challenge led to significant increases in ipsilateral and contralateral secretion weights, ipsilateral histamine levels, ipsilateral NAR, and sneezing. Contralateral histamine levels were not elevated. H1 antagonism with terfenadine markedly reduced the number of sneezes and partially decreased ipsilateral and contralateral secretion weights, without affecting the increase in NAR. Terfenadine premedication also lowered the amount of histamine in ipsilateral secretions after allergen challenge. Performing identical nasal challenges with a 10-fold lower dose of antigen produced similar results. Previous studies showed that terfenadine had no effect on methacholine provocation and completely abolished ipsilateral and contralateral secretion weights after histamine challenge. We conclude that sneezing after allergen challenge is caused almost exclusively by a reflex initiated through H1 receptors and that H1 antagonism has no influence on allergen-induced increases in NAR. Unilateral allergen challenge leads to bilateral increases in secretion weights, which are only partially inhibited by terfenadine, suggesting the involvement of mediators other than histamine in the nasonasal reflex. As reported earlier, terfenadine also decreases allergen-induced histamine release after challenge with the highest dose of antigen.

Cytokines and adhesion molecules in allergic rhinitis.

This review summarizes our current knowledge of nasal allergic inflammation based on studies of cytokines, chemokines, and adhesion molecules in allergic rhinitis. The article also includes some aspects of viral rhinitis. Due to artificial or natural allergen exposure, an increase in the number of eosinophils and basophils, mast cells, IgE-positive cells, macrophages, monocyte-like cells, Langerhans cells, and activated T-cells can be observed within the mucosa and on the mucosal surface. Mediators are known to be released in response to allergens, but do not seem to be adequate to initiate the cell recruitment. After antigen challenge, the release of proinflammatory and regulatory cytokines could be demonstrated, and TH2-type cytokine mRNA upregulation in allergic mucosa has been shown. Proinflammatory cytokines initiate an adhesion cascade and activate T-cells that create an “atopic” cytokine environment within the tissue, which also may be linked to the long-term selective recruitment of eosinophils. However, the acute selective migration of eosinophils after allergen challenge is not fully understood, nor is the role of chemokines in allergic and viral rhinitis. Allergic rhinitis clearly represents an inflammatory reaction.

Comparison of the nasal release of IL-4, IL-10, IL-17, CCL13/MCP-4, and CCL26/eotaxin-3 in allergic rhinitis during season and after allergen challenge.

Background Allergic rhinitis is an inflammatory disease characterized by local overproduction of type 2 cytokines and tissue eosinophilia. Recent research suggests the involvement of additional cytokines such as IL-17, chemokine (C-C motif) ligand (CCL) 26/eotaxin-3, and CCL13/monocyte chemoattractant protein-4 (MCP-4) in its pathophysiology. Furthermore, bronchial epithelial cells treated with IL-17 and type 2 cytokines distinctively up-regulated eotaxin-3 gene expression. In this study we investigated the kinetics of IL-4, IL-10, IL-17, eotaxin-3, and MCP-4 in seasonal allergic rhinitis volunteers after nasal allergen challenge (NAC) and their release during natural pollen exposure. Methods The nasal lavages of 15 symptomatic allergic and 14 nonallergic subjects were collected during the pollination season. Additionally, six allergic subjects underwent a single unilateral nasal allergen and control challenge out of season, and nasal secretions were collected. Levels of IL-4, IL-10, IL-17, eotaxin-3, and MCP-4 in nasal lavages and secretions were measured using an electrochemiluminescent assay. Results After NAC, allergic subjects had a significant immediate response of nasal symptoms as well as a significant increase at 5 hours of IL-4, IL-10, and IL-17 and at 2, 5, and 24 hours significantly raising levels of eotaxin-3. IL-17 and eotaxin-3 concentrations at 5 hours were correlated (r = 0.94; p = 0.005). During natural pollen exposure, barely detectable levels of IL-17 in allergic subjects were also correlated with eotaxin-3 (r = 0.62; p = 0.01). Eotaxin-3 and MCP-4 levels were significantly elevated 9- or 3.7-fold, respectively, and IL-10 and, unexpectedly, IL-4 were significantly lower in allergic subjects compared with nonallergic subjects. Conclusion Nasal IL-17, MCP-4, and, possibly, eotaxin-3 may aggravate and IL-10 may alleviate nasal mucosal allergy.