RESUMEN
Allergen-specific immunotherapy (SIT, desensitization) is applied monthly with subcutaneous injections (SCIT) or sublingually (SLIT) with droplets or tablets on a daily basis. Numerous immunological changes during SIT induce long-lasting tolerance. Efficacy has been demonstrated by a number of controlled studies for insect venom hypersensitivity (SCIT), allergic rhinoconjunctivitis (SCIT, SLIT particularly in grass pollen allergy), and allergic asthma (SCIT > SLIT). SIT is indicated in children and adults with severe allergic reactions from insect venoms (e.g., bee, wasp) or cumbersome symptoms from pollen, house dust mites or mold allergens and proven immediated-type allergy. Contraindications must be considered individually. SIT is performed for 3 years, in case of venom allergy 3-5 years. Severe systemic reactions are rare after SCIT. After SLIT rather local allergic symptoms of short duration occur in the mouth and throat. At present, the number prescriptions for SIT has decreased due to inadequate reimbursement of allergy-related services (diagnostics, therapies, monitoring). In the future, inferior medical care of allergic patients in Germany is expected, who until now have benefited from the preventive effects of SIT (reduced risk of developing asthma and new allergic sensitizations).
Asunto(s)
Alérgenos/inmunología , Especificidad de Anticuerpos/inmunología , Desensibilización Inmunológica/métodos , Epítopos/inmunología , Hipersensibilidad/inmunología , Hipersensibilidad/terapia , Administración Sublingual , Adolescente , Adulto , Alérgenos/administración & dosificación , Niño , Preescolar , Ahorro de Costo , Estudios Transversales , Desensibilización Inmunológica/economía , Alemania , Humanos , Hipersensibilidad/epidemiología , Inyecciones Subcutáneas , Programas Nacionales de Salud/economía , Garantía de la Calidad de Atención de Salud/economía , Mecanismo de Reembolso/economíaRESUMEN
OBJECTIVE: Allergic rhinitis, a disease that impairs quality of life, is characterized by inflammation due to an allergic reaction. Fexofenadine is a second-generation histamine receptor blocker well known for its potent interaction with this inflammatory process. The main aim of this study was to further clarify the anti-inflammatory effects exerted by fexofenadine in patients with intermittent allergic rhinitis. METHODS: Twenty patients with intermittent allergic rhinitis due to birch and mugwort pollen were enrolled. Fexofenadine was administered once a day at a dose of 120 mg. Clinical improvement was assessed by a symptom score, and nasal airway flows were measured by anterior rhinomanometry at baseline and after 2 weeks of treatment with fexofenadine. Nasal smears were tested for eosinophils and nasal lavage fluid were examined for histamine, cysteinyl leukotrienes, soluble intercellular adhesion molecule-1, eosinophil cationic protein, and albumin by enzyme-linked immunosorbent assay. All the tests were performed during the pollen season. RESULTS: Fexofenadine induced a significant improvement in nasal and ocular symptoms (P < .001), nasal edema and secretion (P < .001), and nasal airway flow (P < .001). The clinical improvement was related to a significant reduction in all inflammatory mediators (P < .01 in all cases). CONCLUSION: This study demonstrates that fexofenadine is able to mediate significant changes in different nasal lavage markers from patients with intermittent allergic rhinitis. The changes observed in the markers analyzed in both nasal secretions and serum are attributable to the anti-inflammatory effects of fexofenadine in vivo.
Asunto(s)
Antiinflamatorios/administración & dosificación , Mediadores de Inflamación/inmunología , Líquido del Lavado Nasal/inmunología , Rinitis Alérgica Estacional/tratamiento farmacológico , Terfenadina/análogos & derivados , Adulto , Anciano , Antiinflamatorios/efectos adversos , Antígenos de Plantas/efectos adversos , Antígenos de Plantas/inmunología , Artemisia/inmunología , Betula/inmunología , Progresión de la Enfermedad , Proteína Catiónica del Eosinófilo/análisis , Femenino , Histamina/análisis , Humanos , Mediadores de Inflamación/análisis , Molécula 1 de Adhesión Intercelular/análisis , Leucotrieno D4/análisis , Masculino , Persona de Mediana Edad , Líquido del Lavado Nasal/química , Polen/efectos adversos , Polen/inmunología , Rinitis Alérgica Estacional/inmunología , Terfenadina/administración & dosificación , Terfenadina/efectos adversos , Resultado del TratamientoRESUMEN
BACKGROUND: Neurotrophins are produced by various cells upon different stimuli and participate in the initiation and regulation of inflammation in various diseases including allergy and asthma, but little is known about the production and control of neurotrophins by dendritic cells (DCs). The aim of this study was to assess whether DCs produce the neurotrophins nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), and whether inflammatory stimuli or allergens are able to induce the production of neurotrophic factors. METHODS: Monocyte-derived dendritic cells (MoDCs) were generated from different donors. The neurotrophins NGF and BDNF were demonstrated by RT-PCR, Western blotting, flow cytometry analysis and fluorescence microscopy. MoDCs were cultured and stimulated with lipopolysaccharide (LPS) or allergen for 24 h. The supernatants and cells were collected. Measurement for NGF and BDNF was performed by ELISA. RESULTS: DCs express mRNA for the neurotrophins NGF and BDNF. Proteins were detectable by Western blot, FACS analysis and fluorescence microscopy. LPS led to an up-regulation of BDNF, while NGF was unaffected. Cell lysates demonstrated an increased amount of BDNF after stimulation with LPS or allergen, while NGF was not affected significantly. CONCLUSIONS: DCs are a source of neurotrophins. LPS selectively regulates the production of BDNF. Allergen stimulation leads to an LPS-independent regulation. This contributes to a complex involvement of neurotrophins in allergic diseases.
Asunto(s)
Alérgenos/farmacología , Factor Neurotrófico Derivado del Encéfalo/biosíntesis , Células Dendríticas/metabolismo , Hipersensibilidad/sangre , Lipopolisacáridos/farmacología , Factor de Crecimiento Nervioso/biosíntesis , Western Blotting , Factor Neurotrófico Derivado del Encéfalo/genética , Diferenciación Celular , Células Cultivadas , Células Dendríticas/efectos de los fármacos , Células Dendríticas/patología , Citometría de Flujo , Humanos , Microscopía Fluorescente , Monocitos/patología , Factor de Crecimiento Nervioso/genética , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Regulación hacia ArribaRESUMEN
BACKGROUND: Asthma is a chronic disease defined by airway inflammation, increased airway hyperresponsiveness and episodes of airway obstruction. Although there are abundant clinical and experimental data showing that stress may worsen asthma, the mechanisms linking stress to asthma are not well understood. By inducing a pro-inflammatory cytokine milieu, stress might enhance airway inflammation in bronchial asthma. We therefore investigated the correlation of stress perception and the cytokine profile of circulating lymphocytes in humans. METHODS: Allergic asthmatic patients and healthy controls were evaluated for perceived level of stress, demographic and lung function data. Whole blood cells were obtained and stimulated by mitogen to assess intracellular IL-4, IFN-gamma and TNF-alpha by flow cytometry. Neurotrophins nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) were measured in serum. RESULTS: Asthmatic patients showed significantly higher percentages of TNF-alpha-producing T cells than healthy controls. Only in asthmatic patients was stress perception correlated with percentages of TNF-alpha-producing T cells and serum BDNF levels, while forced expiratory volume in 1 s (% predicted) was negatively correlated to BDNF. CONCLUSION: The results of our study support the hypothesis that stress deteriorates bronchial asthma by inducing a pro-inflammatory cytokine profile in allergic asthmatics. Stress management might provide a supplement therapy of allergic asthma.
Asunto(s)
Asma/inmunología , Citocinas/sangre , Factores de Crecimiento Nervioso/sangre , Hipersensibilidad Respiratoria/inmunología , Estrés Fisiológico/complicaciones , Adulto , Anciano , Asma/diagnóstico , Factor Neurotrófico Derivado del Encéfalo/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factor de Crecimiento Nervioso/sangre , Hipersensibilidad Respiratoria/diagnóstico , Estrés Fisiológico/diagnóstico , Linfocitos T/inmunologíaRESUMEN
BACKGROUND: Neurotrophins are involved in inflammatory reactions influencing several cells in health and disease including allergy and asthma. Dendritic cells (DCs) play a major role in the induction of inflammatory processes with an increasing role in allergic diseases as well. OBJECTIVE: The aim of this study was to investigate the influence of neurotrophins on DC function. METHODS: Monocyte-derived dendritic cells were generated from allergic and non-allergic donors. Neurotrophin receptors were demonstrated by western blotting, flow cytometry and fluorescence microscopy. Activation of small GTPases was evaluated by pull-down assays. DCs were incubated with nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) and supernatants were collected for measurement of IL-4, IL-6, IL-10, IL-12p70, TNF-alpha and TGF-beta. RESULTS: Receptor proteins were detectable by western blot, fluorescence activated cell sorting analysis and fluorescence microscopy. Signalling after neurotrophin stimulation occurred in a ligand-specific pattern. NGF led to decreased RhoA and increased Rac activation, while BDNF affected RhoA and Rac activity in a reciprocal fashion. Cells of allergics released a significantly increased amount of IL-6, while for healthy subjects a significantly higher amount of IL-10 was found. CONCLUSION: These data indicate that DCs are activated by the neurotrophins NGF and BDNF by different pathways in a receptor-dependant manner. These cells then may initiate inflammatory responses based on allergic sensitization releasing preferred cytokines inducing tolerance or a T-helper type 2 response.
Asunto(s)
Factor Neurotrófico Derivado del Encéfalo/farmacología , Células Dendríticas/efectos de los fármacos , Factor de Crecimiento Nervioso/farmacología , Antígenos CD/metabolismo , Western Blotting , Ligando de CD40/farmacología , Diferenciación Celular/efectos de los fármacos , Células Cultivadas , Citocinas/farmacología , Células Dendríticas/citología , Células Dendríticas/metabolismo , Relación Dosis-Respuesta a Droga , Citometría de Flujo , Expresión Génica/efectos de los fármacos , Humanos , Hipersensibilidad/sangre , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Lipopolisacáridos/farmacología , Monocitos/citología , Monocitos/efectos de los fármacos , Monocitos/metabolismo , Poli I-C/farmacología , Receptor trkA/genética , Receptor trkA/metabolismo , Receptor trkB/genética , Receptor trkB/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Linfocitos T/citología , Linfocitos T/efectos de los fármacos , Linfocitos T/metabolismo , Proteínas de Unión al GTP rac/metabolismo , Proteínas de Unión al GTP rho/metabolismoRESUMEN
BACKGROUND: Omalizumab, a recombinant monoclonal anti-immunoglobulin E (IgE) antibody, shows proven efficacy in the treatment of allergic diseases. A little is known about the immunological pathways affected by the decrease of circulating free IgE during omalizumab treatment. AIM OF THE STUDY: To investigate the immunological consequence of IgE withdrawal, we studied the influence of omalizumab on stimulated IgE-release of cultured peripheral blood mononuclear cells (PBMC) and on the relative number of lymphocytes in the peripheral blood (cellular immune status) in patients with allergic asthma. METHODS: Nineteen patients were enrolled and received omalizumab at a dose of at least 0.016 mg/kg/IgE (IU/ml) every 4 weeks. PBMC were isolated from peripheral blood. Cells were cultured and stimulated with IL-4 (5 ng/ml) and CD40 ligand (1 microg/ml) for 10 days. IgE release was detected in cell culture supernatants by enzyme-linked immunosorbent assay (ELISA). Cellular immune status was investigated by fluorescence-activated cell sorting. RESULTS: Omalizumab treatment induced significant inhibition of stimulated IgE release (median 1.38-0 ng/ml vs. 1.64-2.0 ng/ml in placebo group, P<0.05). B-lymphocyte counts were also significantly lower in the omalizumab group compared with placebo after 12 weeks of treatment (median 18.2-15.6% lymphocytes vs 12.7-13.7% lymphocytes after placebo, P<0.01). There were no significant differences in the other lymphocyte subpopulations between the groups. CONCLUSIONS: These findings provide evidence of immunological influences of omalizumab treatment, leading to a downregulation of IgE secretion and decrease of lymphocyte subpopulations (B-cells) indicating their anti-inflammatory potency.
Asunto(s)
Alérgenos/efectos adversos , Alérgenos/inmunología , Antiinflamatorios no Esteroideos/uso terapéutico , Anticuerpos Monoclonales/farmacología , Asma/inmunología , Asma/terapia , Inmunidad Celular , Inmunoglobulina E/metabolismo , Adulto , Anciano , Anticuerpos Antiidiotipos , Anticuerpos Monoclonales Humanizados , Asma/metabolismo , Femenino , Humanos , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/metabolismo , Masculino , Persona de Mediana Edad , OmalizumabRESUMEN
Elevated serum levels of antigen-specific immunoglobulin (Ig)E are often associated with allergic respiratory diseases. This parallel-group, randomised, double-blind, placebo-controlled trial was designed to study the influence of omalizumab on the early nasal response to allergen challenge reflected by symptom score and inflammatory marker levels in nasal lavage fluid (NAL). A total of 23 patients with allergic rhinitis took part in the study, 11 were given placebo and omalizumab was administered subcutaneously in 12. Omalizumab or placebo were given at 2- or 4-week intervals based on a patient's body weight and IgE levels to a total dose of 0.016 mg x kg(-1) x IgE(-1) (IU x mL(-1)) every 4 weeks. Compared to placebo, 16 weeks of treatment with omalizumab significantly inhibited allergen challenge-induced nasal symptoms (median symptom score 7.0-0.5 versus 7.0-7.0) and inhibited the increase of human serum albumin (median 15.3-0.12 mg x mL(-1) versus 8.2-19.7 mg x mL(-1)) in the NAL after allergen challenge. Treatment with omalizumab induced a significant decrease in tumour necrosis factor-alpha levels in basal NAL, but no change was seen for histamine. These results indicate that subcutaneously administered monoclonal anti-immunoglobulin-E antibody, omalizumab, inhibits the nasal responses to allergen challenge of patients with allergic rhinitis. Omalizumab may provide a new strategy for the treatment of allergic rhinitis.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Rinitis Alérgica Perenne/tratamiento farmacológico , Adulto , Alérgenos/inmunología , Anticuerpos Antiidiotipos , Anticuerpos Monoclonales Humanizados , Citocinas/análisis , Método Doble Ciego , Femenino , Histamina/análisis , Humanos , Inmunoglobulina E/inmunología , Masculino , Líquido del Lavado Nasal/química , Líquido del Lavado Nasal/inmunología , Pruebas de Provocación Nasal , Omalizumab , Rinitis Alérgica Perenne/inmunología , Albúmina Sérica/análisisRESUMEN
BACKGROUND: Recent studies have shown that neurotrophins are produced by and can act on several immune-inflammatory cells. The origin of circulating as well as local neurotrophins is unknown. OBJECTIVES: The aim of this study was to assess whether eosinophils of allergic and non-allergic donors produce, store and release the neurotrophic factors NGF, BDNF and NT-3. METHODS: Eosinophils were purified by negative immunoselection (purity > 96%) from allergic asthmatics and non-allergic donors (25 to 53 years). The presence of mRNA for neurotrophic factors was evaluated by reverse transcription PCR. Specificity was demonstrated by cloning products and sequencing. Stored NGF, BDNF and NT-3 was demonstrated by Western-blotting and flow cytometry. Eosinophils were incubated and supernatants were collected for measurement of neurotrophic factors after cell stimulation with PAF. Neurotrophin content in eosinophil lysates was determined by ELISA. RESULTS: Eosinophils demonstrate mRNA for neurotrophins. Proteins were detectable by Western blot and FACS analysis. Neurotrophins were found in the eosinophil lysates at different amounts comparing allergic and non-allergic donors. Cell stimulation with PAF (10-8-10-5 M) after priming with GM-CSF leads to a dose-dependant release of NGF and BDNF. CONCLUSIONS: Eosinophils store, produce and release NGF, BDNF and NT-3. They are a possible source of elevated neurotrophin levels found in allergy and asthma.
Asunto(s)
Asma/sangre , Eosinófilos/metabolismo , Factores de Crecimiento Nervioso/sangre , Adulto , Western Blotting , Factor Neurotrófico Derivado del Encéfalo/sangre , Factor Neurotrófico Derivado del Encéfalo/genética , Células Cultivadas , Femenino , Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Factores de Crecimiento Nervioso/genética , Neurotrofina 3/sangre , Neurotrofina 3/genética , ARN Mensajero/genética , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
The aim of the present study was to determine the effect of treatment with omalizumab, an anti-immunoglobulin E antibody, on asthma-related quality of life (AQoL) in patients with moderate-to-severe allergic asthma. A total of 546 patients with allergic asthma were randomised to double-blind subcutaneous treatment with either placebo or omalizumab for 52 weeks. A constant beclomethasone dipropionate dose was maintained during the first 16 weeks (steroid-stable phase). This was followed by a 12-week steroid-reduction phase. The core study was followed by a 24-week double-blind extension phase. AQoL was evaluated at baseline and at the end of the steroid-stable (week 16), steroid-reduction (week 28) and extension phases (week 52) using the Juniper Asthma Quality of Life Questionnaire (AQLQ). Baseline AQLQ scores were comparable for the two treatment groups. Relative to placebo, omalizumab-treated patients demonstrated statistically significant improvements from baseline across all four AQLQ domains, as well as overall AQoL score, at weeks 16 (except environmental exposure), 28 and 52. Patients on omalizumab were also more likely to achieve clinically significant improvements in AQoL during the course of the study. Overall, almost 70% of patients and investigators rated treatment with omalizumab as "excellent/good", compared with approximately 40% of placebo recipients. Clinical studies show that omalizumab enhances disease control whilst reducing corticosteroid consumption in patients with allergic asthma. The results of the present study show that these changes are paralleled by improvements in asthma-related quality of life that are meaningful to such patients.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Asma/tratamiento farmacológico , Calidad de Vida , Administración por Inhalación , Adolescente , Adulto , Anciano , Antiinflamatorios/administración & dosificación , Anticuerpos Antiidiotipos , Anticuerpos Monoclonales Humanizados , Asma/inmunología , Asma/fisiopatología , Beclometasona/administración & dosificación , Niño , Método Doble Ciego , Femenino , Volumen Espiratorio Forzado , Glucocorticoides/administración & dosificación , Humanos , Inmunoglobulina E/sangre , Inmunoglobulina E/inmunología , Inyecciones Subcutáneas , Masculino , Persona de Mediana Edad , Omalizumab , Ápice del Flujo EspiratorioRESUMEN
BACKGROUND: Recent studies have shown that nerve growth factor (NGF) can act on several immune cells as well as residential cells. But little is known about their role in modulating eosinophil function via activation of high-affinity receptors. OBJECTIVES: The aim of this study was to assess whether eosinophils express functional receptors and if their function is influenced by NGF, brain-derived neurotrophic factor (BDNF) or neurotrophin-3 (NT-3). METHODS: Eosinophils were purified by negative immunoselection (purity > 96%). High-affinity neurotrophin receptors were demonstrated by reverse transcription polymerase chain reaction, western blotting and flow-cytometry analysis. Functionality of receptors was demonstrated by receptor phosphorylation after ligand binding. Eosinophils were incubated with NGF, BDNF and NT-3, and cells and supernatants were collected for measurement of the mediators IL-4, IL-5, IL-8, transforming growth factor (TGF)-beta1, eosinophil cationic protein (ECP), eosinophil protein X (EPX) as well as eosinophil viability. RESULTS: Eosinophils expressed mRNA for neurotrophin receptors. Proteins were detectable by western blot and fluorescent-activated cell sorter analysis. The receptors were phosphorylated after stimulation with neurotrophins. After NGF stimulation, a significant increase in IL-4 was detectable. BDNF and NT-3 stimulation led to a significant increase in EPX. Eosinophil viability was not influenced. CONCLUSIONS: Eosinophils express the functionally active receptors TrkA, TrkB and TrkC. Receptor activation stimulates eosinophils. This might be an additional pathway regulating inflammatory responses in allergic reactions.
Asunto(s)
Eosinófilos/metabolismo , Factores de Crecimiento Nervioso/farmacología , Receptores de Factor de Crecimiento Nervioso/metabolismo , Rinitis Alérgica Perenne/inmunología , Western Blotting , Factor Neurotrófico Derivado del Encéfalo/farmacología , Citometría de Flujo , Humanos , Mediadores de Inflamación/análisis , Neurotrofina 3/farmacología , Fosforilación , ARN Mensajero/análisis , Receptor trkA/genética , Receptor trkA/metabolismo , Receptor trkB/genética , Receptor trkB/metabolismo , Receptor trkC/genética , Receptor trkC/metabolismo , Receptores de Factor de Crecimiento Nervioso/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Estadísticas no ParamétricasRESUMEN
BACKGROUND: The neurotrophins Nerve Growth Factor (NGF), Brain-Derived Neurotrophic Factor (BDNF) and Neurotrophin (NT)-3 are produced, stored and released by various immunological cells. The influence of NTs upon the function of these cells is described. Elevated plasma levels were found in inflammatory, autoimmune and allergic diseases with the highest levels in allergic asthma. A connection between bronchial hyper-responsiveness and serum levels has been reported. OBJECTIVE: Little is known about the influence of treatment with inhaled corticosteroids (ICS) on serum NT levels and their influence on the asthmatic state. METHODS: Eighty-seven volunteers were studied. Thirty-eight were stable allergic asthmatics with constant ICS doses, 29 were asthmatics not receiving anti-asthmatic treatment and 20 were age- and sex-matched healthy controls. Demographic and lung function data were evaluated. NT serum levels were determined by ELISA. RESULTS: NGF and BDNF levels were significantly increased in untreated asthmatics compared to the control and the treated group, while NT-3 demonstrated significantly higher levels in treated asthmatics compared to healthy controls. After stabilization of untreated subjects with ICS, the NT levels decreased significantly. CONCLUSIONS: These results suggest that NTs participate in allergic inflammation and asthma. Effective treatment leads to a decrease of circulating neurotrophic factors.
Asunto(s)
Corticoesteroides/uso terapéutico , Asma/tratamiento farmacológico , Asma/inmunología , Circulación Sanguínea/efectos de los fármacos , Circulación Sanguínea/inmunología , Factor Neurotrófico Derivado del Encéfalo/sangre , Factor Neurotrófico Derivado del Encéfalo/efectos de los fármacos , Factor de Crecimiento Nervioso/sangre , Factor de Crecimiento Nervioso/efectos de los fármacos , Neurotrofina 3/sangre , Neurotrofina 3/efectos de los fármacos , Hipersensibilidad Respiratoria/tratamiento farmacológico , Terapia Respiratoria , Adulto , Femenino , Volumen Espiratorio Forzado/efectos de los fármacos , Volumen Espiratorio Forzado/fisiología , Humanos , Pulmón/irrigación sanguínea , Pulmón/efectos de los fármacos , Masculino , Valores de Referencia , Pruebas de Función RespiratoriaRESUMEN
OBJECTIVE AND DESIGN: There is evidence that substance P (SP) is involved in events related to allergic and nonallergic rhinitis. Furthermore, some effects of SP seem to be greater in subjects suffering from allergic rhinitis than in nonallergic subjects. To investigate if these effects may be partly mediated by histamine release (HR) we studied the influence of SP on HR from nasal mucosa of subjects with and without allergic rhinitis using an in vitro organ culture system. SUBJECTS: Nasal mucosa of the inferior turbinate was obtained from ten patients suffering from allergic rhinitis and eighteen non-allergic subjects receiving surgical therapy for nasal obstruction. METHODS: Tissue samples of nasal mucosa were stimulated with 10(-5) M SP or with 10(-5) M Ca-ionophore A23187 for 120 minutes, and the histamine content was determined in the culture supernatant. RESULTS: Both SP and Ca-ionophore A23187, caused a significantly higher HR from the samples of the non-allergic group (p < 0.01) compared to baseline controls (spontaneous release). The same effect was seen in the allergic group (p < 0.01 and p = 0.036). Comparing the increase in HR from allergic and non-allergic mucosa, in allergics the HR stimulated by SP was significantly higher (p = 0.031), whereas Ca-ionophore A23187 did not show this effect. CONCLUSION: These findings suggest a role of SP in inducing release of histamine from human nasal mucosa, thereby influencing physiologic and pathophysiologic nasal conditions, especially in allergic inflammatory processes.