[Significance of cytokines and chemokines in infections of the upper respiratory tract].
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Chemokines↗
Biomedical subjects
C Rudack
Publications and source records attributed to C Rudack.
Glucocorticosteroids rapidly inhibit allergen-induced expression of E-selectin in vitro in a mucosal model of allergic rhinitis.
BACKGROUND: Transendothelial migration of cells to sites of inflammation is a hallmark of the allergic reaction. The adhesion cascade involves the initial expression of the adhesion molecule E-selectin on endothelial cells. The aim of the study was to determine the efficacy of a 30-min preincubation of the glucocorticosteroids (GCS) fluticasone, prednisolone, and fluocortin butyl on allergen- and interleukin (IL)-1beta-induced E-selectin expression in allergic rhinitis. METHODS: Freshly taken nasal inferior turbinate mucosa of 19 subjects with allergic rhinitis was cut into small cubes and preincubated for 30 min with prednisolone (n = 6), fluticasone (n = 5), and fluocortin butyl (n = 3) in different concentrations, followed by allergen exposure at a concentration of 1000 BU/ml for 1 and 2 h. Additionally, fluticasone-preincubated tissues were exposed to recombinant human rhIL-1beta (n = 5) at a concentration of 2 pg/ml. The expression of E-selectin was assessed by immunohistochemistry (APAAP technique) and computerized image evaluation. RESULTS: In this model, E-selectin expression was significantly upregulated by allergen and rhIL- 1beta within 1 and 2 h. After 30-min preincubation with prednisolone and fluocortin butyl at drug concentrations of 10-8 mol/1, we found a significant (> or = 50%) reduction of the E-selectin expression after 1 and 2 h. Allergen-induced E-selectin expression was nearly abolished at concentrations of 10-5 (prednisolone) and 10-4 mol/l (fluocortin butyl). Fluticasone significantly inhibited E-selectin expression by > or = 50% at concentrations of 10-14 and 10-12 mol/l after 1 and 2 h, and abolished E-selectin induction at concentrations of 10-12 and 10-10 mol/l, respectively. Exposure of mucosal cubes to rhIL-lbeta (n = 5) also induced rapid upregulation of E-selectin expression, an effect which could be only partially suppressed by fluticasone preincubation at concentrations of 10-l0 mol/l. CONCLUSIONS: Allergen-induced E-selectin expression is significantly and rapidly inhibited by GCS preincubation, fluticasone being more potent than prednisolone and fluocortin butyl. We suggest that this rapid effect is mainly indirect, possibly by inhibition of allergen-induced cytokine release.
Adolescent↗
[Effect of cytokines and fibroblasts on eosinophilic granulocyte survival in polyposis nasi].
BACKGROUND: Eosinophilic infiltration is the most prominent histologic feature of nasal polyps. The effects of eosinophil-associated cytokines and fibroblast derived factors on survival of isolated eosinophils from blood of patients with nasal polyps were investigated. METHODS AND PATIENTS: Peripheral blood eosinophils of 9 patients with nasal polyps were incubated in 1. culture medium alone and in a medium containing, 2. IL-5 (10 pg/ml); 3. IL-3, IL-5, GM-CSF (10 pg/ml); 4. supernatants of fibroblasts cultured from polyps of the same 9 patients; and 5. supernatants of fibroblasts enriched with IL-5, -3, and GM-CSF. Viability of eosinophils was assessed by their ability to take up WST-1. RESULTS: The survival index (T50) of eosinophils cultured in different culture medium is listed as follows: 1. medium alone: 0.8 +/- 0.14 days (MV +/- SEM), 2. medium containing IL-5; 1.2 +/- 0.19 days, 3. medium containing IL-3, IL-5, and GM-CSF: 3.1 +/- 0.13 days, 4. fibroblast supernatants: 1.6 +/- 0.29 days, and in 5. fibroblast supernatants enriched with IL-3, IL-5 and GM-CSF: 2.2 +/- 0.21 days. CONCLUSION: IL-5, prolongs eosinophil survival in vitro, IL-3, IL-5 and GM-CSF revealed synergistic effects; survival of eosinophils was significantly prolonged in comparison to stimulation with IL-5 alone. Supernatants of fibroblasts also prolonged eosinophil survival. This effect is probably due to GM-CSF, which was found in high concentrations in fibroblast supernatants.
Cell Count↗
[Cytokines and chemokines in paranasal sinus diseases].
BACKGROUND: New insights into inflammatory processes became possible by investigating the pattern of cytokines and chemokines as well as adhesion molecules in different acute and chronic sinus diseases since the last decade. This review aims to update and discuss findings of in vitro and in vivo studies concerning the role of cytokines and chemokines in inflammatory sinus diseases during the last years. RESULTS: Discrepancies in research findings may be due to the small available databases today, the use of different techniques for investigation, and the lack of a valuable classification of sinus diseases. Despite this discrepancies, there is evidence that in acute bacterial and viral sinusitis, proinflammatory cytokines play a dominant role in initiating and sustaining the inflammation, which is especially characterized by neutrophil tissue infiltration. In chronic sinusitis IL-3 dominates the cytokine profile, giving support to a variety of inflammatory cells. IL-3 may also contribute to fibrosis and constant thickening of the mucosa leading to an obstruction of the ostiomeatal complex. In most bilateral nasal polyps, tissue eosinophilia is a striking finding which is believed to play a central role in pathogenesis, as it does in asthma. Eosinophilia may be explained by increased migration and prolonged eosinophil survival. Activation and survival of eosinophils in nasal polyps are thought to be regulated by autocrine stimulation by IL-5. Therefore, IL-5 represents the main target for future therapy in nasal polyposis. CONCLUSIONS: Defining cytokine and chemokine patterns in inflammatory sinus diseases leads to a better understanding of immunologic processes in nasal mucosa. Results of cytokine and chemokine research are of paramount interest in developing new therapeutic approaches.
Cell Adhesion Molecules↗
Effect of prednisolone on cytokine synthesis in nasal polyps.
To investigate steroid effects on eosinophils and their associated cytokines in nasal polyps, we sampled nasal polyp tissue from 20 subjects during routine surgery. Freshley removed polyps were cut into small pieces and incubated in culture medium for 24 h in different concentrations of prednisolone (10(-2)-10(-6) mol/L). Cell viability was assessed by means of trypan dye exclusion of the supernatants. The number of eosinophils was quantified by means of cytocentrifuge smears stained by May-Giemsa-Grunwald stain. The cytokine protein content of interleukin-5 (IL-5), IL-3, and granulocyte-macrophage colony-stimulating factor (GM-CSF) was measured by ELISA technique in supernatants and in homogenates of nasal polyp tissue. Our results revealed a significant reduction in the number of eosinophils and total number of vital cells at concentrations of 10(-3) and 10(-2) mol/L. GM-CSF and IL-5 protein levels were significantly reduced in supernatants and in homogenates after treatment with prednisolone, whereas IL-3 synthesis was not diminished. Corticosteroid effects known to inhibit synthesis of eosinophil-associated cytokines could be measured in terms of a significant decrease in IL-5 and GM-CSF protein level as well as in a decrease in the number of vital cells.
Cell Survival↗
[Cytokine pattern in various forms of sinusitis].
BACKGROUND: Inflammatory sinus diseases include acute sinusitis, chronic purulent sinusitis, and chronic polypoid rhinosinusitis. We investigated the cytokine profile of different types of rhinosinusitis in order to evaluate whether a distinct form of rhinosinusitis is associated with the expression of a specific cytokine profile. METHODS AND PATIENTS: Fresh sinus mucosa obtained during routine surgery from patients with acute sinusitis (n = 10), chronic sinusitis (n = 7), antrochoanal polyp (n = 10), nasal polyps (n = 8), and controls of turbinate mucosa (n = 7) were homogenized. The cytokine protein content (IL-1 beta,IL-3,IL-5,IL-6,IL-8,GM-CSF) of tissue homogenates was measured using ELISA technique. RESULTS: In the group of proinflammatory cytokines, the protein levels measured for interleukin IL-8, a proinflammatory cytokine, IL-1 beta, and IL-6 were elevated in acute sinusitis. In the group of eosinophil-activating cytokines interleukin-3, -5 and granulocyte an makrophage-colony stimulating factor, we measured a significantly elevated protein level of IL-5 in nasal polyp tissue in contrast to significantly elevated IL-3 protein level in chronic sinusitis. CONCLUSIONS: These findings suggest that IL-8 plays a pivotal role in neutrophil-dominated and IL-5 in eosinophil-dominated sinusitis. IL-3 seems to sustain chronic inflammation.
Biopsy↗
The role of cytokines in infectious sinusitis and nasal polyposis.
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Bacterial Infections↗
[Treatment of tinnitus with lidocaine? A report of clinical experiences].
The efficacy of intravenous lidocaine therapy in patients suffering from severe tinnitus aurium has been reported for many years although pharmacological mechanisms for its use are not fully understood. In order to evaluate the effectiveness of lidocaine therapy in the treatment of tinnitus we performed a retrospective study on 77 patients suffering from tinnitus. All patients were given a test dose of lidocaine after a saline placebo infusion. Suppression of tinnitus was classified according to a visual analogue scale. Our results showed that 19 of the 77 patients investigated experienced different degrees of reduced tinnitus. Fourteen of these latter patients also were treated with oral tocainide 3 x 400 mg/day. Treatment was stopped in 13 of the patients because of side-effects or an insufficient effect on tinnitus. Our findings suggest that lidocaine and tocainide do not have a significant role in pharmacological treatment of tinnitus except in certain cases of long-standing severe tinnitus.
Administration, Oral↗
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.
Adult↗
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-alpha (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-1 beta, TNF-alpha 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-1ra) 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.
Cell Adhesion Molecules↗
[Immunology of the inner ear].
Immunological mechanisms may play an important role in the pathogenesis of such inner ear disorders as sudden or rapidly progressive sensorineural hearing loss. As the human inner ear remains unaccessible for immunological studies in clinical practice, the pathogenesis of a possible immune-mediated disease affecting the inner ear still is unclear. Most immunological studies are performed in animal models or concentrate on clinical laboratory tests with patients' blood samples. Experimental data from animal models has shown that the inner ear is capable of immunoprotection by recognizing and processing antigen. Its answer to a local antigen challenge is an immune response with immunoglobulin synthesis. Clinical data from systemic disease have revealed that immune-mediated processes are involved in the pathogenesis of vestibulocochlear disorders. However, a specific testing system for identifying possible antigens or antibodies involved in inner ear diseases is still not available.
Animals↗
Cytokines in nasal polyposis, acute and chronic sinusitis.
Cytokines are potent biologic factors involved in the regulation of inflammation, immune defense, and wound healing. Recently, growing interest has developed in the role of cytokines in chronic sinusitis and nasal polyposis. In the present study, we investigated the cytokine profile of different types of rhinosinusitis in order to evaluate whether a specific form of rhinosinusitis is associated with the expression of a certain cytokine profile. Sinus mucosa from patients with acute sinusitis (n = 10), chronic sinusitis (n = 7), antrochoanal polyp (n = 10), nasal polyps (n = 8) and controls of turbinate mucosa (n = 7) were sampled. The cytokine protein content (IL-1 beta, IL-3, IL-4, IL-5, IL-6, IL-8, IL-13, GM-CSF, interferon-gamma) of tissue homogenates was measured using ELISA technique. In acute sinusitis, the synthesis of proinflammatory cytokines and of the neutrophil chemokine IL-8 and IL-3 appeared to be upregulated. Chronic sinusitis mucosa demonstrated no significantly increased concentrations of the measured cytokines. In bilateral nasal polyposis, but not in antrochoanal polyps, the eosinophil related cytokine IL-5 was strongly upregulated. From these findings, it appears that specific cytokine patterns are found in different forms of sinusitis, and that IL-5 may represent the most important cytokine responsible for tissue eosinophilia in nasal polyposis.
Acute Disease↗