leukotriene-b4 and Rhinitis--Allergic--Seasonal

The allergic process is believed to consist of two phases: early and late. The early phase reaction is mainly induced by histamine released from mast cells. Histamine binding specific cell receptors produces clinical allergic symptoms. This mediator also activates neutrophils and eosinophils as well as being a chemoattractant for these cells. Histamine increases IL-8 level and evokes leukocyte rolling on endothelial cells. Thus histamine participates in both early and late-phase allergic responses.

Topics: Binding Sites; Chemoreceptor Cells; Eosinophils; Histamine; Humans; Inflammation Mediators; Interleukin-8; Leukotriene B4; Mast Cells; Neutrophils; Receptors, Histamine; Rhinitis, Allergic, Seasonal

Allergic rhinitis symptoms of itching, sneezing, rhinorrhea, and nasal obstruction significantly decrease patients' quality of life. Compared with histamine and leukotriene receptor antagonists, the petasol butenoate complex Ze 339 displays pharmacologically distinct properties. In vitro it inhibits the biosynthesis of leukotrienes and mediator release from activated eosinophils.. This study aimed to assess the efficacy and mode of action of Ze 339, desloratadine, and placebo on allergic rhinitis symptoms, nasal airflow, and local mediator levels after unilateral nasal allergen provocation.. In this double-blind, randomized, crossover study 18 subjects with allergic rhinitis to grass pollen received Ze 339, desloratadine, and placebo for 5 days before nasal allergen challenge with grass pollen extract. Rhinomanometry, symptom assessment, and local inflammatory mediator measurement were performed during the 24 hours after allergen challenge.. With Ze 339, the patient's time to recovery (5.4 ± 1.6 hours) from nasal obstruction after allergen challenge (time for return to 90% of baseline value ± SEM) was significantly shorter than with placebo (9.1 ± 2.3 hours, P = .035) and desloratadine (10.7 ± 2.5 hours, P = .022). Likewise, Ze 339's standardized symptom assessment for nasal obstruction (3.2 ± 1.3 hours) showed significantly faster relief (time for return to baseline value ± SEM compared with placebo, 8.3 ± 2.4 hours; P = .027) and desloratadine (4.5 ± 1.2 hours, P = .030). One interesting finding was that Ze 339 significantly reduced IL-8 and leukotriene B(4) levels in nasal secretions before challenge.. When compared with desloratadine and placebo, Ze 339 shows better efficacy in relieving nasal obstruction symptoms and inhibiting critical components of the chemokine network and as such represents a novel symptomatic and possible prophylactic treatment for allergic rhinitis.

Topics: Adult; Allergens; Anti-Allergic Agents; Bronchial Provocation Tests; Chemokines; Cross-Over Studies; Cytokines; Double-Blind Method; Female; Humans; Interleukin-8; Leukotriene B4; Loratadine; Male; Middle Aged; Nasal Obstruction; Plant Extracts; Pollen; Rhinitis, Allergic, Seasonal; Young Adult

Airway hyperresponsiveness and inflammation can be noninvasively studied by bronchial provocation using direct (histamine) or indirect (adenosine 5'-monophosphate [AMP]) stimuli and induced sputum.. To report on the immediate effects of histamine and AMP challenge on induced sputum neutrophil counts and related mediator levels.. We performed a single-masked, randomized, placebo-controlled, 3-way, crossover, methodological study in 14 atopic patients (median age, 25 years; 8 males; mean +/- SD forced expiratory volume in 1 second, 99% +/- 5%) without anti-inflammatory medication use. At baseline, sputum induction was performed. Bronchial challenges with AMP, histamine, or placebo were performed 48 hours later. Thirty minutes after challenge, sputum induction was performed again. Challenge periods in each patient were separated by more than 2 weeks. Sputum cells and the mediators leukotriene B4, interleukin 8, myeloperoxidase, and albumin were quantified.. Comparing median challenge-induced relative changes in cells and mediators, neither histamine nor AMP challenge altered the induced sputum neutrophil counts (histamine, 2.7%; AMP, 2.95%; placebo, -2%; P > .07 for all), interleukin 8 levels (histamine, 2.4 ng/mL; AMP, -3.8 ng/mL; placebo, -0.2 ng/mL; P > .06), leukotriene B4 levels (histamine, -4.8 pg/mL; AMP, 3 pg/mL; placebo, 6 pg/mL; P > .08), or myeloperoxidase levels (histamine, 0.16 microg/mL; AMP, 0 microg/mL; placebo, -0.03 microg/mL; P > .07). Sputum albumin levels were increased after histamine challenge compared with AMP and placebo challenge (P < .01 for both).. Histamine and AMP provocation have no major effects on induced neutrophil counts and related mediator levels in atopic patients, whereas histamine challenge induces plasma leakage. Potential interactions of noninvasive methods to evaluate airway reactivity and inflammation should be carefully considered.

Topics: Adenosine Monophosphate; Adult; Asthma; Bronchial Provocation Tests; Cell Count; Cross-Over Studies; Female; Histamine; Humans; Interleukin-8; Leukotriene B4; Male; Neutrophils; Peroxidase; Rhinitis, Allergic, Seasonal; Sputum

The clinical importance of leukotrienes in human allergy has not been defined, in part because there have been no selective 5-lipoxygenase inhibitors that have been effective and safe for use in humans. To address the hypothesis that stimulated leukotriene synthesis causes symptoms of immediate-hypersensitivity reactions in vivo, I investigated the effects of a new 5-lipoxygenase inhibitor, A-64077, on provoked allergic nasal symptoms and mediator release in a double-blind, randomized, placebo-controlled study. Eight subjects with allergic rhinitis underwent nasal challenge on two occasions after an oral dose of 800 mg of A-64077 or an identical-appearing placebo.. Allergen-induced nasal congestion was significantly attenuated (P less than 0.02) by A-64077; peak levels of leukotriene B4 (median, 684 pg per milliliter) and 5-hydroxyeicosatetraenoic acid (median, 704 pg per milliliter) in nasal-rinse fluids were markedly reduced (to 67 and 185 pg per milliliter, respectively; P less than 0.01), whereas levels of prostaglandin D2 were not. Histamine release and sneezing were not reduced significantly by A-64077, but there was a significant correlation (P less than 0.01) between the changes in these variables within subjects. The mean (+/- SEM) stimulated synthesis of leukotriene B4 in whole blood ex vivo was markedly reduced by A-64077 (from 153 +/- 19 to 20 +/- 9 ng per milliliter, P less than 0.01), and the specificity of A-64077 for 5-lipoxygenase inhibition was verified by its lack of effect on the synthesis of serum thromboxane B2 or 12-hydroxyeicosatetraenoic acid.. These results provide direct evidence of an important role for the 5-lipoxygenase products of arachidonic acid in allergic rhinitis and support the notion that further experiments in this area may lead to new therapeutic approaches to allergic disorders.

Topics: Double-Blind Method; Female; Histamine Release; Humans; Hydroxyeicosatetraenoic Acids; Hydroxyurea; Leukotriene B4; Leukotrienes; Lipoxygenase Inhibitors; Male; Nasal Obstruction; Nasal Provocation Tests; Prostaglandin D2; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Sneezing

Accumulating evidence confirms the presence of pan-airway inflammation in allergic rhinitis patients. Smoking is known to affect the asthmatic airway inflammation. However, no study has evaluated the impact of smoking on airway inflammation of allergic rhinitis patients.. The aim of the present study was to evaluate the impact of smoking on inflammatory and oxidative stress biomarkers in patients with seasonal allergic rhinitis, using non-invasive methods for sample collection.. Forty patients with seasonal allergic rhinitis (20 smokers and 20 non-smokers) and 30 healthy subjects (15 smokers and 15 non-smokers) were recruited for the study during pollen season. All subjects were submitted to measurement of the fraction of exhaled NO (FeNO), exhaled breath condensate (EBC) collection, nasal lavage collection, pre- and post- bronchodilation spirometry and metacholine bronchial challenge testing. pH, leukotriene B(4) (LTB(4)) and 8-isoprostane were determined in EBC and nasal lavage samples.. Patients with allergic rhinitis presented higher LTB(4) and 8-isoprostane levels in nasal lavage (P<0.0001 for both comparisons), with no significant differences between smokers and non-smokers. Patients with allergic rhinitis also presented higher LTB(4) levels and lower pH in EBC (P<0.001 and P=0.004, respectively), with prominent differences between smokers and non-smokers (P<0.0001 and P=0.003, for LTB(4) and pH, respectively). A significant correlation between nasal lavage and EBC LTB(4) values was observed (r(s)=0.313, P=0.048).. Patients with allergic rhinitis present increased LTB(4) and 8-isoprostane in their nasal cavity, however, with no significant differences between smokers and non-smokers. In contrast, smokers with allergic rhinitis present higher LTB(4) levels and lower pH in EBC, suggesting that these patients may be more susceptible to the deleterious effects of smoking, compared with non-smokers.

Topics: Adult; Biomarkers; Breath Tests; Dinoprost; Eosinophils; Female; Humans; Hydrogen-Ion Concentration; Immunoglobulin E; Inflammation; Leukotriene B4; Male; Nasal Lavage Fluid; Nitric Oxide; Oxidative Stress; Rhinitis, Allergic, Seasonal; Smoking

Allergic rhinitis and bronchial asthma can coexist and affect each other.. To investigate the relationship between the postseasonal increase in the concentration of leukotriene (LT) B4 and LTE4 in exhaled breath condensate (EBC) and bronchial responsiveness to methacholine (BRM) in patients with seasonal allergic rhinitis (SAR).. In 28 patients with SAR and 50 healthy study patients, the leukotrienes were measured in EBC during and after the pollen season by gas chromatography/mass spectrometry. The BRM was determined after the pollen season.. In 7 patients with SAR, significantly increased concentrations of both the leukotrienes were found in EBC during and 5 months after the pollen season. The following seasonal and postseasonal median values were measured in patients with SAR in comparison with control patients: LTB4: 131 and 90 pg/mL vs 80 and 79 pg/mL, P < .001 and P = .03, respectively; LTE4: 122 and 86 pg/mL vs 76 and 74 pg/mL, P < .001 and P = .02, respectively. Five months after the pollen season, the concentrations of LTB4 and LTE4 decreased with respect to their seasonal values (90 and 86 pg/mL, respectively, P < .001, for both leukotrienes). In 7 patients with SAR and leukotriene levels exceeding the reference limits, significantly increased BRM was also found (LTB4: P = .02; LTE4: P = .002).. The seasonal and postseasonal increases in LTB4 and LTE4 concentrations in EBC of the patients with SAR correlated significantly with the later increase in BMR. This relationship could provide a useful predictive parameter for early inflammatory processes in the lower airways of patients with allergic rhinitis.

Topics: Adult; Anti-Asthmatic Agents; Asthma; Bronchi; Exhalation; Female; Humans; Leukotriene B4; Leukotriene E4; Male; Methacholine Chloride; Middle Aged; Reference Standards; Rhinitis, Allergic, Seasonal; Young Adult

Leukotrienes (LTs) are increased in exhaled breath condensate (EBC) in patients with asthma. So far no data have been reported about LT levels in nonasthmatic patients with seasonal allergic rhinitis (SAR). The aim of the study was to find out whether the LT levels in EBC were increased in the nonasthmatic adult patients with SAR both during and after the pollen season in comparison with healthy controls and to assess the changes of the LT levels after the pollen season.. Twenty-nine nonasthmatic adult patients with SAR underwent measurement of exhaled LTs in the EBC during and after the pollen season. Leukotrienes B(4), C(4), D(4) and E(4) were analysed by a specific and sensitive gas chromatography/mass spectrometry (GC/MS) assay and compared with 50 healthy nonsmoking controls. Spirometry, skin prick tests and nonspecific IgE were evaluated.. Leukotrienes concentrations (B(4), E(4) but not D(4)) were significantly increased in and after the pollen season in patients with SAR in comparison with healthy controls. In most of the samples, LT C(4) was undetectable. The values of all exhaled LTs were significantly decreased after the pollen season compared with the seasonal baseline: LTB(4) (P = 0.023), LTD(4) (P = 0.020), LTE(4) (P = 0.047).. Levels of exhaled LTB(4) and LTE(4) were higher in SAR patients than in healthy controls and decreased after the pollen season as compared with levels in season. The SAR patients with the highest in season LT levels had also the post-season levels elevated and this may be an early marker of inflammatory process in the lower airways despite the absence of clinical symptoms of asthma.

Topics: Adolescent; Adult; Case-Control Studies; Exhalation; Female; Humans; Leukotriene B4; Leukotriene E4; Male; Middle Aged; Osmolar Concentration; Pollen; Rhinitis, Allergic, Seasonal; Seasons

Allergic rhinitis is a common disease characterized by the symptoms of pruritus, sneezing, hypersecretion and nasal blockage. Increased mucosal barrier permeability has been suggested to be an indicator for the severity of allergic rhinitis. This study investigates the passage of radiolabelled albumin from the nasal mucosal circulation into the lumen in guinea pigs intraperitoneally sensitized and intranasally challenged with antigen. In order to characterize the allergic rhinitis model, we evaluated a number of potential influencing factors in nasal plasma exudation, including antigen doses, volumes of antigen solution used, and animal position during the nasal lavage, and the conditions of nasal lavage. The number of eosinophils and levels of histamine and leukotriene B4 in the nasal lavage and eosinophils in the nasal mucosa were determined at the early and late phases after antigen challenge. We also compared the effects of topical nasal treatments for allergic rhinitis on nasal inflammatory responses. Our results demonstrate that, in the guinea pig nasal mucosa, topical challenge with antigens induces plasma exudation and histamine release at the acute-phase reaction, and plasma exudation and eosinophil infiltration at the late-phase reaction. These changes are similar to those reported in human allergic rhinitis. Alterations of nasal plasma exudation, histamine release and eosinophil influx were dependent upon the concentrations and volumes of antigens. An antihistamine inhibited the acute-phase reaction partially, whereas budesonide inhibited effects at the late-phase reaction. We suggest that this model of guinea pig allergic rhinitis with the early and late responses may be useful for high-throughout screening of new drugs.

Topics: Administration, Topical; Animals; Anti-Allergic Agents; Eosinophils; Exudates and Transudates; Guinea Pigs; Histamine; Leukotriene B4; Mast Cells; Microscopy, Electron; Nasal Lavage Fluid; Nasal Mucosa; Rhinitis, Allergic, Seasonal

Allergic rhinitis is an inflammatory disease associated with local leukotriene release during periods of symptoms. Zileuton, a leukotriene synthesis inhibitor, is known to inhibit the release of leukotriene B4. Because we previously showed that leukotriene B4 is a potent mediator of neutrophil-dependent nasal secretion, we investigated whether Zileuton inhibited allergen-induced nasal secretion. Using a newly developed method for isolating and superfusing a nasal segment, we examined the effect of Zileuton on nasal secretion and neutrophil recruitment in ragweed-sensitized dogs. Instillation of ragweed into the nasal segment caused time-dependent increases in the volume of airway fluid and the recruitment of neutrophils. Zileuton prevented ragweed-induced neutrophil recruitment and nasal secretion. These results indicate that leukotrienes are important mediators of allergy-induced nasal secretion in dogs. Future clinical studies in allergic patients will determine whether there is a therapeutic role for leukotriene synthesis inhibitors in modulating neutrophil recruitment and hypersecretion in the nose.

Topics: Animals; Dogs; Hydroxyurea; Hypersensitivity; Leukotriene Antagonists; Leukotriene B4; Nasal Mucosa; Nasal Obstruction; Nasal Provocation Tests; Neutrophils; Plants; Pollen; Rhinitis, Allergic, Seasonal; Time Factors

Allergen challenge in some patients with respiratory allergy is followed by an early and a late reaction.. To evaluate the duration of mediator release and inflammatory cell recruitment during the late antigen-induced nasal response.. Eight patients with seasonal allergic rhinitis due to grass pollen underwent local challenge with the relevant allergen, a non-relevant allergen (Parietaria judaica), and nebulized saline solution. Nasal lavages were performed at baseline and 6, 24, 48, 72 h after challenge. Eosinophil cationic protein (ECP), leukotriene C4 (LTC4), leukotriene B4 (LTB4) myeloperoxidase (MPO) and prostaglandin D2 (PGD2) levels were radioimmunoassayed and histamine concentration was measured by an automated fluorometric method.. Nasal challenge with the relevant antigen induced a response 6 h after stimulation, which subsided within 24 h. Eosinophilia, observed in the nasal lavages collected from 6 to 24 h after this challenge, was accompanied by ECP release. Neutrophilia were found in the nasal lavages collected from 6 to 24 h after challenge. The increase in neutrophil number correlated with MPO levels and LTB4 concentrations, but not with the intensity of nasal obstruction. Antigen challenge also induced significant recruitment of mononuclear cells 48 h after provocation. The challenge significantly raised histamine, but not PGD2, levels in the nasal lavages collected 6 h after provocation. A trend towards an increase in LTC4 levels in the nasal lavages collected 6 h after specific antigen challenge was also found. Nasal challenge with a non-relevant allergen or with saline solution did not cause either inflammatory cell recruitment or mediator release.. Nasal challenge with the relevant antigen can induce a late response characterized by local accumulation of eosinophils, neutrophils and mononuclear cells persisting for 48 h and accompanied by release of ECP, MPO, LTB4 and histamine. These results indicate that a single antigen challenge in patients with allergic rhinitis causes prolonged inflammatory alterations which may contribute to the development of airway hyperreactivity.

Topics: Adolescent; Adult; Antigens; Blood Proteins; Chemotaxis, Leukocyte; Eosinophil Granule Proteins; Eosinophils; Female; Histamine; Humans; Leukocytes, Mononuclear; Leukotriene B4; Leukotriene C4; Male; Nasal Lavage Fluid; Nasal Provocation Tests; Neutrophils; Peroxidase; Pollen; Prostaglandin D2; Radioimmunoassay; Rhinitis, Allergic, Seasonal; Ribonucleases

Leukotriene B4 (LTB4), a potent chemokinetic mediator for neutrophils, is enhanced by interleukin-8 (IL-8) and may play a key role in the inflammatory response of asthma.. The aim of the present study was to investigate whether zileuton, a 5-lipoxygenase antagonist known to inhibit LTB4 production and recruitment of eosinophils/neutrophils in bronchoalveolar fluid, could affect the production of LTB4 and IL-8 by allergen-stimulated peripheral blood mononuclear cells in vitro from patients with asthma and/or allergic rhinitis.. Peripheral blood mononuclear cells were isolated using Ficoll-Hypaque density gradient from 14 subjects (2 with asthma, 11 with asthma and allergic rhinitis, and 1 with allergic rhinitis) and were stimulated by selected allergens (grass, tree, mite, and mold) in the absence or presence of 1 and 10 microM of zileuton. Supernatants were collected and assayed for LTB4 and IL-8 levels using RIA and ELISA, respectively.. Levels of LTB4 were significantly elevated in peripheral blood mononuclear cells stimulated with mold, grass, and tree compared with the unstimulated control group (P<.05). Levels of IL-8 were significantly elevated in all allergen-stimulated peripheral blood mononuclear cells, except mold, compared with the unstimulated control group (P<.05). Zileuton significantly reduced production of LTB4 by mold and tree-stimulated peripheral blood mononuclear cells. By contrast, no effect of zileuton on IL-8 production was observed in allergen-stimulated peripheral blood mononuclear cells.. The zileuton-induced attenuation of LTB4 production by allergen-stimulated peripheral blood mononuclear cells from patients with asthma and/or allergic rhinitis occurs independently from the allergen-stimulated IL-8 production.

Topics: Adult; Aged; Allergens; Asthma; Female; Humans; Hydroxyurea; Interleukin-8; Leukocytes, Mononuclear; Leukotriene B4; Lipoxygenase Inhibitors; Male; Middle Aged; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal

Nasal challenge with platelet activating factor (PAF) is able to induce local neutrophilia, with a different degree of responsiveness in atopic subjects and in nonatopic subjects. We investigated whether nasal accumulation of neutrophils induced by PAF is accompanied by the release of neutrophil-derived mediators.. Nasal lavages were performed before and after challenge with PAF (500 nmol), lyso-PAF (500 nmol), and saline solution in 10 patients with allergic rhinitis and 10 normal subjects to evaluate changes in neutrophil counts and the release of myeloperoxidase (MPO) and immunoreactive leukotriene B4.. PAF caused neutrophilia, which appeared after 30 minutes in atopic subjects and after 3 hours in nonatopic subjects. Furthermore, when compared with saline insufflation, PAF caused a significant release of MPO in the nasal lavage fluids collected 30 minutes, 3 hours, and 24 hours after challenge in atopic subjects and 3 hours after challenge in nonatopic subjects, with higher values in the former than in the latter. Neutrophil counts correlated with MPO levels in the nasal lavages collected after PAF challenge. A lower degree of neutrophilia was found 3 hours after stimulation with lyso-PAF in both groups of subjects, with a marginal release of MPO in atopic subjects only. No significant increase of immunoreactive leukotriene B4 levels in nasal lavages was found after challenge with either PAF or lyso-PAF.. These results indicate that PAF-induced neutrophilia in the nose is accompanied by the release of MPO, which appears earlier and is more marked in atopic subjects than in nonatopic subjects.

Topics: Administration, Intranasal; Adult; Female; Humans; Hypersensitivity, Immediate; Leukocyte Count; Leukocytosis; Leukotriene B4; Male; Nasal Lavage Fluid; Neutrophils; Peroxidase; Platelet Activating Factor; Rhinitis, Allergic, Seasonal; Sodium Chloride

We determined the relationship of allergic disease to the number and activity of eosinophils and their production of leukotriene B4 and leukotriene C4 (leukotriene D4 equivalents). Granulocytes from allergic rhinitis (AR) subjects and asthmatics release more LTC4 than normals. Furthermore, eosinophils of asthmatics generate more LTC4 than those of AR subjects.

Topics: Adult; Asthma; Calcimycin; Eosinophils; Female; Granulocytes; Humans; Leukocyte Count; Leukotriene B4; Male; Middle Aged; Reference Values; Rhinitis, Allergic, Seasonal; SRS-A; Statistics as Topic

Studies have demonstrated that increased amounts of histamine in the airways of asthmatic patients are associated with increased airway reactivity. However, using routine bronchoalveolar lavage (BAL), histamine can be detected in only a portion of asthmatic subjects and a minority of control populations. To obtain relevant mediators from the airways in higher concentrations by avoiding the dilution inherent with a standard BAL, a technique was developed to lavage isolated airway segments of the human lung that employed a double-lumen bronchoscope and a balloon-tipped catheter. Lavage fluid obtained by this method yielded significantly higher concentrations of histamine than that obtained with routine BAL (asthmatic subjects, 2,403 +/- 633 pg/ml vs 188 +/- 42 pg/ml; rhinitis subjects, 533 +/- 187 pg/ml vs 113 +/- 53 pg/ml; normal subjects, 174 +/- 63 pg/ml vs 11 +/- 11 pg/ml). Similar findings were also noted for prostaglandin D2 (PGD2). Segmental airway lavage also resulted in higher lavage fluid concentrations of LTB, than routine BAL. Segmental airway lavage should help in studying the relationship of mast cell degranulation to airways reactivity in both asthmatic and other study populations.

Topics: Adolescent; Adult; Asthma; Bronchial Provocation Tests; Bronchoalveolar Lavage Fluid; Bronchoscopes; Bronchoscopy; Catheterization; Histamine; Humans; Leukotriene B4; Methacholine Chloride; Methacholine Compounds; Middle Aged; Prostaglandin D2; Rhinitis, Allergic, Seasonal; Therapeutic Irrigation

Lyso-PAF-acether and PAF-acether (formerly platelet-activating factor) were detected in nasal secretions from patients with hay fever who underwent local antigen challenge. Lyso-PAF release was observed in 12 of 13 patients, with a maximum (p less than 0.001) 5 min after stimulation and a progressive decrease during the first hour. PAF was detected in the 5-min postchallenge nasal washings from two of 13 subjects. After HPLC, this mediator was found in four of seven postchallenge nasal washings submitted to this procedure, with a peak 5 min and 10 min after provocation. Histamine analysis revealed a significant (p less than 0.001) but time-limited (5 min) release in nasal secretion. The pattern of immunoreactive leukotriene C4 showed a maximal peak (p less than 0.01) 5 min after allergen provocation, with raised levels for 20 min. Nasal stimulation with nebulized saline solution or grass pollens in healthy subjects and in patients suffering from allergic rhinitis caused by Dermatophagoides pteronyssinus was followed by no local mediator release. These data indicate that, in addition to histamine and peptide-leukotrienes, lyso-PAF and PAF are released in nasal secretions after local antigen stimulation in patients with hay fever, with a preponderance of lyso-PAF response. On the basis of these results, it is conceivable that these ether-phospholipids may be involved in allergic inflammation of human nasal airways.

Topics: Adult; Chromatography, High Pressure Liquid; Female; Histamine; Humans; Leukotriene B4; Male; Nasal Mucosa; Nasal Provocation Tests; Platelet Activating Factor; Pollen; Radioallergosorbent Test; Rhinitis, Allergic, Seasonal; Skin Tests; Therapeutic Irrigation

The release kinetics of histamine and leukotrienes C4 (LTC4) and B4 (LTB4) were investigated in nasal secretions of 10 patients with hay fever after antigen challenge. High levels of biologically active histamine were found in nasal washes from asymptomatic allergic and normal subjects. With repeated lavages, the amount of histamine recovered dropped markedly. Grass pollen challenge was followed by a significant (p less than 0.05) dose-dependent and time-limited (5 min) increase in histamine level in 7 of 10 patients; these values, however, were lower than those found in basal conditions. In 8 of 10 patients with hay fever, antigen challenge induced a significant (p less than 0.05) dose-dependent increase in LTC4 level, which persisted for 30 min. The LTC4 generation was well correlated with the appearance of allergic symptoms; LTB4 production was found in 2 patients only. A different pattern of symptoms was observed after in vivo nasal stimulation with histamine and LTC4. Histamine caused sneezing, itching, rhinorrhea, and nasal obstruction; conversely, the main symptom induced by LTC4 was a more pronounced and longer lasting nasal obstruction.

Topics: Adult; Chromatography, High Pressure Liquid; Histamine; Humans; Leukotriene B4; Pollen; Rhinitis, Allergic, Seasonal; SRS-A

Leukotrienes are a recently discovered group of arachidonic acid-derived lipid mediators. Using radioimmunoassay and high pressure liquid chromatography (HPLC), we have identified the SRS-A sulphidopeptide leukotrienes (LTC4, LTD4 and LTE4) in nasal washings from patients with allergic rhinitis who underwent nasal challenge with specific allergen. Smaller, but significant, amounts of LTB4 were also detected. The concentrations of nasal leukotrienes were directly related to the dose of allergen, and were recovered in washings in a time-dependent fashion after challenge. When the patients were subjected to methacholine nasal challenge on a control day, we found only negligible amounts of either the sulphidopeptide leukotrienes or LTB4. These findings support the view that LTC4, LTD4 and LTE4 might contribute to the pathogenesis of allergic rhinitis as a result of their recognized effects on mucous hypersecretion and vasopermeability, and that the potent chemoattractant LTB4 might be involved in the subsequent infiltration of inflammatory cells.

Topics: Adult; Animals; Antigens; Humans; Leukotriene B4; Methacholine Compounds; Middle Aged; Mites; Nasal Provocation Tests; Pollen; Radioimmunoassay; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; SRS-A