leukotriene-c4 and Rhinitis--Allergic--Seasonal

Cysteinyl-leukotrienes (cysteinyl-LTs), that is, LTC4, LTD4, and LTE4, trigger contractile and inflammatory responses through the specific interaction with G protein-coupled receptors (GPCRs) belonging to the purine receptor cluster of the rhodopsin family, and identified as CysLT receptors (CysLTRs). Cysteinyl-LTs have a clear role in pathophysiological conditions such as asthma and allergic rhinitis (AR), and have been implicated in other inflammatory conditions including cardiovascular diseases, cancer, atopic dermatitis, and urticaria. Molecular cloning of human CysLT1R and CysLT2R subtypes has confirmed most of the previous pharmacological characterization and identified distinct expression patterns only partially overlapping. Interestingly, recent data provide evidence for the immunomodulation of CysLTR expression, the existence of additional receptor subtypes, and of an intracellular pool of CysLTRs that may have roles different from those of plasma membrane receptors. Furthermore, genetic variants have been identified for the CysLTRs that may interact to confer risk for atopy. Finally, a crosstalk between the cysteinyl-LT and the purine systems is being delineated. This review will summarize and attempt to integrate recent data derived from studies on the molecular pharmacology and pharmacogenetics of CysLTRs, and will consider the therapeutic opportunities arising from the new roles suggested for cysteinyl-LTs and their receptors.

Topics: Adult; Animals; Asthma; Cardiovascular Diseases; Child; Child, Preschool; Dermatitis, Atopic; Female; Humans; Hydroxyurea; Leukotriene Antagonists; Leukotriene C4; Leukotriene D4; Leukotriene E4; Membrane Proteins; Pharmacogenetics; Receptors, Leukotriene; Receptors, Purinergic; Recombinant Proteins; Rhinitis, Allergic, Seasonal; SRS-A; Tissue Distribution

Cysteinyl leukotrienes (CysLTs: LTC4, LTD4, and LTE4) are a family of potent inflammatory mediators that appear to contribute to the pathophysiologic features of allergic rhinitis. Because treatment with a CysLT1 receptor antagonist and a 5-lipoxygenase inhibitor modified allergen-induced nasal blockage in patients with allergic rhinitis, and CysLTs were detected in nasal cavity lavage fluid, it has been suggested that CysLTs act as significant inflammatory mediators in allergic rhinitis. The role of CysLTs was evaluated in our experimental allergic rhinitis model in sensitized guinea pigs which shows biphasic nasal blockage, sneezing and nasal hyperresponsiveness to LTD4 induced by repetitive inhalation challenge with Japanese cedar pollen. In this model, the CysLT1 receptor antagonist pranlukast suppressed the late-phase nasal blockage but not early blockage and sneezing. Nasal hyperresponsiveness (nasal blockage) to LTD4 was largely blocked by pranlukast, naphazoline, and N omega-nitro-L-arginine-methyl ester. The results demonstrate that nasal blockage induced by CysLTs is mainly due to dilatation of nasal blood vessels, which can be induced by the nitric oxide produced through CysLT1 receptor activation. On the other hand, when pollen inhalation challenge was performed in the presence of nasal hyperresponsiveness, antigen-induced biphasic nasal blockage and sneezing were considerably enhanced and CysLTs contributed to both symptoms, suggesting that nasal hyperresponsiveness induces aggravation of antigen-induced nasal symptoms. The results presented in this study further suggest that our model is a good representative of human allergic rhinitis and offer evidence that CysLTs are chemical mediators mainly responsible for allergic nasal symptoms.

Topics: Allergens; Animals; Bronchial Provocation Tests; Chromones; Cryptomeria; Disease Models, Animal; Guinea Pigs; Humans; Inflammation Mediators; Leukotriene Antagonists; Leukotriene C4; Leukotriene D4; Leukotriene E4; Lipoxygenase Inhibitors; Membrane Proteins; Pollen; Receptors, Leukotriene; Rhinitis, Allergic, Seasonal

To investigate the effect of omalizumab, a humanized monoclonal antibody, in addition to specific immunotherapy (SIT) on in vitro sulfidoleukotriene release (SLT) (A) before, (B) directly after, and (C) 1 yr after treatment with omalizumab. Children and adolescents (6.3-17.6 yr) with sensitization to birch and grass pollens and suffering from seasonal allergic rhinitis were included in a Phase III, placebo-controlled, multicenter clinical study. Within the four-arm study, patients were randomly chosen to receive SIT for either birch or grass pollen and either subcutaneous omalizumab or placebo for 24 wk during the pollen season. Thereafter, omalizumab or placebo treatment ended, but SIT therapy continued. Blood samples were collected from 92 (A, B) and 78 children (C), respectively. Leukocytes were isolated and stimulated with grass and birch pollen allergens. In the supernatants, SLT (LTC4, LTD4, LTE4) were measured using ELISA [cellular allergen stimulation test, DPC-Biermann, Germany]. At the end of treatment the combination of omalizumab + SIT-grass [median SLT-release: 2125 (before) and 416 ng/ml (after omalizumab treatment); p < 0.001] as well as omalizumab + SIT-birch [1404 and 207 ng/ml; p < 0.001] resulted in significantly lower SLT release after stimulation with the corresponding allergen compared to placebo + SIT-grass [2231 and 2490 ng/ml] or placebo + SIT-birch [1324 and 2489 ng/ml]. One year after omalizumab or placebo treatment, there was no significant difference in SLT release between the 4 groups (omalizumab + SIT-grass: 2855; SIT-grass + placebo: 2543; omalizumab + SIT-birch: 2417; SIT-birch + placebo: 2573 ng/ml). These results strongly suggest that the observed effects of decreased SLT release after omalizumab treatment were attributable to the treatment with omalizumab, rather than to SIT therapy.

Topics: Adolescent; Allergens; Anti-Allergic Agents; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Betula; Child; Combined Modality Therapy; Drug Monitoring; Female; Germany; Humans; Immunotherapy; Injections, Subcutaneous; Leukocytes; Leukotriene C4; Leukotriene D4; Leukotriene E4; Leukotrienes; Male; Omalizumab; Poaceae; Rhinitis, Allergic, Seasonal; Time Factors; Treatment Outcome

Histamine antagonists together with topical steroids are the treatment of choice in allergic rhinitis. Many of these histamine antagonists exhibit effects in addition to blockade of the histamine receptor. In this study we have investigated the effects of ebastine and carebastine on the release of eicosanoids and cytokines from human dispersed polyp cells and the effect of these compounds on the release of inflammatory mediators into nasal lavage fluid after allergen challenge. Ebastine was shown to block the release of anti-IgE-induced prostaglandin D2 (PGD2) and leukotriene C4/D4 from human nasal polyp cells (IC30 values of 2.57 and 9.6 mumol/L, respectively) and to inhibit the release of cytokines. Carebastine inhibited the release of PGD2 (IC30 8.14 mumol/L) but had little effect on cytokine release. When patients underwent nasal provocation tests with allergen, ebastine significantly increased the mean number of pollen grains required to induce an allergic response. In addition, the drug inhibited the release of granulocyte-macrophage colony-stimulating factor but had no effect on any other mediators measured.

Topics: Adolescent; Adult; Allergens; Butyrophenones; Cross-Over Studies; Double-Blind Method; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Histamine H1 Antagonists; Humans; Leukotriene C4; Male; Middle Aged; Nasal Polyps; Piperidines; Pollen; Prostaglandin D2; Rhinitis, Allergic, Seasonal

The aim of this study was to evaluate the effects of the new anti-allergic drug, N-acetyl-aspartyl-glutamate (ZY15106), on allergen-induced nasal symptoms and mediator release. Fifteen outpatients suffering from seasonal allergic rhinitis due to grass pollen were included in the study. A nasal antigen challenge followed by evaluation of symptoms was performed in basal conditions. Ten of the 15 patients underwent sequential nasal lavages in order to evaluate allergen-induced mediator release. The study was performed in winter, when the patients were symptom free, and was a randomized single-blind crossover trial of a 6% solution of ZY15106 (daily dosage: 48 mg) versus placebo (lactose). The drug and the placebo were administered intranasally q.i.d. for 1 week, with a 2-week interval between the two treatments. Treatment with ZY15106, but not with placebo, caused a significant reduction in nasal obstruction in the first 30 min after challenge and at 60 min and itching in the first 10 min after challenge, but did not reduce sneezing and rhinorrhoea. Moreover, ZY15106 significantly reduced the histamine release in 5 min postchallenge lavage (4.5 ng.ml-1 after placebo administration vs 2.5 ng.ml-1, after treatment with ZY15106). A reduction in immunoreactive LTC4 release in the 5 and 10 min post-challenge lavages was observed after ZY15106 administration (placebo vs active treatment: at 5 min 2.9 ng.ml-1 vs 1.4 ng.ml-1; at 10 min: 2.25 ng.ml-1 vs 0.9 ng.ml-1).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Dipeptides; Female; Histamine H1 Antagonists; Histamine Release; Humans; Leukotriene C4; Male; Rhinitis, Allergic, Seasonal; Single-Blind Method; Therapeutic Irrigation

The aim of the study was to investigate the effect of short-term treatment with fluticasone propionate on the response to nasal allergen challenge in patients with allergic rhinitis. Responses to nasal allergen challenge were assessed subjectively by recording symptom scores on visual analogue scales, and objectively by measuring histamine, PGD2 and LTC4 in nasal lavage and by measuring nasal inspiratory peak flow following challenge. Nasal allergen challenge resulted in an increase in all symptom scores (P < 0.05); an increase in histamine and PGD2 (P < 0.05), and a decrease in nasal inspiratory peak flow at 1 h, 5 h and 7 h following challenge (P < 0.05). The allergen-induced changes in symptom scores, mediator levels and nasal inspiratory peak flow were attenuated by treatment with fluticasone propionate (P < 0.05 for all parameters measured). Post-challenge nasal obstruction was decreased by 45%; sneezing, itching and rhinorrhoea by 73, 78 and 80% respectively in the group as a whole comparing scores whilst on fluticasone propionate with those on no therapy. Fluticasone propionate, 200 micrograms twice daily for 2 weeks is effective in reducing significantly the early and late response to nasal allergen challenge.

Topics: Administration, Intranasal; Adult; Allergens; Androstadienes; Anti-Inflammatory Agents; Female; Fluticasone; Glucocorticoids; Histamine; Humans; Inspiratory Capacity; Leukotriene C4; Male; Middle Aged; Nasal Lavage Fluid; Poaceae; Pollen; Prostaglandin D2; Radioimmunoassay; Rhinitis, Allergic, Seasonal

Leukotrienes (LTs) and prostanoids are potent pro-inflammatory and vasoactive lipid mediators implicated in airway disease, but their cellular sources in the nasal airway in naturally occurring allergic rhinitis (AR) are unclear.. To quantify cellular expression of enzymes of the 5-lipoxygenase (5-LO) and cyclooxygenase (COX) pathways by immunohistochemistry in nasal biopsies from patients with symptomatic perennial AR (PAR, n = 13) and seasonal AR (SAR, n = 14) and from normal subjects (n = 12).. Enzymes of the 5-LO pathway (5-LO, FLAP, LT A4 hydrolase, LTC4 synthase) and the COX pathway (COX-1, COX-2, prostaglandin D2 synthase) were immunostained in glycol methacrylate resin-embedded inferior turbinate biopsy specimens, quantified in the lamina propria and epithelium, and co-localized to leucocyte markers by camera lucida.. In the lamina propria of PAR biopsies, median counts of cells expressing FLAP were fourfold higher than in normal biopsies (Mann-Whitney, P = 0.014), and also tended to be higher than in SAR biopsies (P = 0.06), which were not different from normal. PAR biopsies showed threefold more cells immunostaining for LTC4 synthase compared with SAR biopsies (P = 0.011) but this was not significant compared with normal biopsies (P = 0.2). These changes were associated with ninefold more eosinophils (P = 0.0005) with no differences in other leucocytes. There were no significant differences in the lamina propria in immunostaining for 5-LO, LTA4 hydrolase, COX-1, COX-2 or PGD2 synthase. Within the epithelium, increased expression of COX-1 was evident in PAR biopsies (P = 0.014) and SAR biopsies (P = 0.037), associated with more intra-epithelial mast cells in both rhinitic groups (P < 0.02).. In the nasal biopsies of PAR subjects, increased expression of regulatory enzymes of the cysteinyl-LT biosynthetic pathway was associated with lamina propria infiltration by eosinophils. Seasonal rhinitis biopsies shared only some of these changes, consistent with transient disease. Increased intra-epithelial mast cells and epithelial COX-1 expression in both rhinitic groups may generate modulatory prostanoids.

Topics: 5-Lipoxygenase-Activating Proteins; Adolescent; Adult; Aged; Arachidonate 5-Lipoxygenase; Carrier Proteins; Cyclooxygenase 1; Cyclooxygenase 2; Female; Humans; Intramolecular Oxidoreductases; Leukotriene A4; Leukotriene C4; Leukotrienes; Lipocalins; Male; Membrane Proteins; Middle Aged; Nasal Mucosa; Prostaglandins; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; T-Lymphocyte Subsets; Young Adult

This examination focused on the allergic early and late phase reaction via nasal symptom scores, acoustic rhinometry, and the determination of mediators possibly involved in late phase eosinophilia. We examined nasal secretions for IL-5; the chemokines IL-8, MCP-1, and Eotaxin; the adhesion molecule sVCAM-1, and the leukotriene LTC4 for their suggested impacts on tissue eosinophilia.. 13 patients suffering from seasonal allergic rhinitis were challenged intranasally out of the natural pollen season by their specific allergen. In a time window of 8 h following the provocation, patients completed symptom questionnaires, and underwent acoustic rhinometry. Nasal secretions were gained by the cotton wool method over a time period of 8 h. Nasal secretions were analyzed for the above mentioned mediators.. Individual evaluation of the acoustic rhinometry measurements revealed an early phase reaction in 100 % of the cases and a late phase reaction in 92 %. The need to sneeze and a runny nose were the strongest symptoms during the allergic early and late phase reaction. A typical late phase kinetic was observed for IL-5, MCP-1, Eotaxin, sVCAM-1, and LTC4. IL-8 was characteristic for early phase reaction but increased in late phase as well.. The need to sneeze, a runny nose, and the overall quality of life were most apt to evaluate the allergic early and late phase reaction. Highly significant correlations between nasal obstruction and acoustic rhinometry measurements indicate a high sensitivity of visual analogue scales in the representation of minimal changes in nasal symptom scores during the allergic reaction. Our data point to a relevant role of the TH2 cytokine IL-5; of the chemokines IL-8, MCP-1, and Eotaxin; of the adhesion molecule sVCAM-1, and of the leukotriene LTC4 for the allergic late phase eosinophilia.

Topics: Adult; Chemokine CCL11; Chemokines, CC; Eosinophilia; Female; Humans; Interleukin-5; Interleukin-9; Leukotriene C4; Male; Nasal Mucosa; Nasal Provocation Tests; Rhinitis, Allergic, Seasonal; Rhinometry, Acoustic; Surveys and Questionnaires; Vascular Cell Adhesion Molecule-1

The aim of this study was to evaluate the efficacy and safety of 3 years oral specific immunotherapy in patients with perannial allergic rhinitis and bronchial asthma caused by allergy to mites.. Fifteen patients with allergic perannial rhinitis entered the study. Ten of them suffered also from bronchial asthma. During 3 years of therapy we have monitored the appearance of side effects, clinical parameters (symptoms degree and medication usage score) and immunological parameters (serum eosinophil cationic protein concentration and leukotriene C4 liberation by peripheral blood leukocytes upon in vitro specific allergens stimulation).. We have not observed the appearance of any adverse event, so medication has been recognized as a safe. Moreover, we have observed a lot of positive therapeutical effects--the lowering of symptoms scores, accompanied by advantageous changes in immunological parameters. However, in spite of 3 years of therapy, many patients still reported the substantial clinical symptoms, accompanied by still elevated serum ECP concentration and relatively high leukotriene C4 liberation by peripheral blood leukocytes upon in vitro stimulation by specific allergens.. Oral specific immunotherapy in the patients with allergic diseases of upper airways is a safe medication but leads only to moderate clinical efficacy accompanied by lowering serum ECP concentration and reducing of leukotrienes C4 liberation by peripheral blood leukocytes stimulated by specific allergens.

Topics: Administration, Oral; Adult; Animals; Dermatophagoides pteronyssinus; Eosinophil Cationic Protein; Female; Humans; Immunotherapy; Leukotriene C4; Male; Plant Extracts; Rhinitis, Allergic, Seasonal; Skin Tests

Human eosinophils have been reported to express both the mRNA and protein for the high affinity IgE receptor (FcepsilonRI); it is speculated that this receptor plays a role in eosinophil mediator release in allergic diseases. However, questions still remain. How much of the FcepsilonRI protein is actually expressed on the cell surface of the eosinophil? If they are present, are these IgE receptors associated with effector functions of eosinophils? To address these issues, we studied blood eosinophils from patients with ragweed hay fever. A high level of low affinity IgG receptor (FcgammaRII, CD32), but no expression of FcepsilonRI, was detectable on the eosinophil surface by standard FACS analysis. However, after in vitro sensitization with biotinylated chimeric IgE (cIgE), cell-bound cIgE was detected by PE-conjugated streptavidin. This cIgE binding was partially inhibited by anti-FcepsilonRI mAb, suggesting that eosinophils do express minimal amounts of FcepsilonRI detectable only by a sensitive method. Indeed, FACS analysis of whole blood showed that eosinophils express approximately 0.5% of the FcepsilonRI that basophils express. When stimulated with human IgE or anti-human IgE, these eosinophils did not exert effector functions; there was neither production of leukotriene C4 or superoxide anion nor any detectable degranulation response. In contrast, eosinophils possessed membrane-bound human IgG and showed functional responses when stimulated with human IgG or anti-human IgG. Thus, IgG and/or cytokines, such as IL-5, appear to be more important for eosinophil activation in allergic diseases than IgE.

Topics: Adolescent; Adult; Animals; Antigens, CD; Basophils; Binding Sites, Antibody; Biomarkers; Biotinylation; Cell Degranulation; Eosinophils; Humans; Hypersensitivity; Immunoglobulin E; Leukotriene C4; Lymphocyte Activation; Mice; Middle Aged; Receptors, IgE; Receptors, IgG; Recombinant Fusion Proteins; Rhinitis, Allergic, Seasonal; Superoxides

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

Studies of in vitro eosinophil function are dependent on efficient and reliable methods of cell isolation. Protocols using Percoll or metrizamide density gradients have been of limited use in isolating peripheral blood eosinophils in sufficient numbers and purity from subjects with normal or only slightly elevated eosinophil counts, thereby restricting comparative studies to preparations from hypereosinophilic subjects. Recently, a method utilizing negative selection by anti-CD16 coated magnetic beads has greatly improved eosinophil isolation by dramatically increased yields and purity. However, little is known as to the differential effect of various isolation methods on the functional activity of eosinophils. In this study, eosinophils were isolated by either discontinuous multiple density Percoll gradients or anti-CD16-coated magnetic beads: several functional activities were then compared using cells obtained by the two methods of isolation. Compared with Percoll isolated eosinophils, anti-CD16 bead separated eosinophils had significantly increased baseline and stimulated LTC4 production, spontaneous O2- generation, and expression of specific cell surface markers. No significant difference was observed in the cells' in vitro survival and adhesion. Such differences may be due to the isolation of eosinophils of all densities by anti-CD16 beads, or the effect of neutrophils interacting with the beads to release eosinophil agonists or primers. Alternatively, the Percoll gradient method with the eosinophils' exposure to dextran and Ficoll-Hypaque may affect subsequent cell function. Therefore, comparison of eosinophil function between cells isolated by different protocols must be considered before concluding which is the true measure of in vivo cell function.

Topics: Adolescent; Adult; Antibodies, Monoclonal; Asthma; Cell Adhesion; Cell Separation; Centrifugation, Density Gradient; Colloids; Endothelium, Vascular; Eosinophils; Flow Cytometry; Humans; Immunomagnetic Separation; Leukotriene C4; Middle Aged; Povidone; Receptors, IgG; Rhinitis, Allergic, Seasonal; Silicon Dioxide; Umbilical Veins

By using a microsuction technique, a quantitative determination of chemical mediators in nasal secretions was performed in 18 hay-fever patients and in a control group of 10 healthy volunteers. The authors then compared these quantitative data for mediators with objective nasal findings counting the number of sneezes, passive anterior rhinomanometry (PAR) and nasal inspiratory peak flow. A sampling protocol was designed with a follow-up of 3 days after nasal allergen challenge (NAC) in order to investigate both early and late allergic reactions. Median baseline concentrations of five major mediators were obtained: histamine, 19 ng/g; leukotriene C4 (LTC4), 5.7 ng/g. tryptase, 0; prostaglandin D2 (PGD2), 477 pg/g; eosinophil cationic protein (ECP), 105 ng/g. Significant increases in histamine (214 ng/g), LTC4 (20 ng/g) and tryptase (28 microU/g) were found, but a significant decrease occurred in ECP (47 ng/g) and PGD (226 pg/g) immediately after NAC in the patients studied. Most ECP concentrations (94%) increased slowly 1 h after NAC and reached a significantly higher level 24 h later. In evaluating nasal symptoms, sneezes were present in a high percentage of cases (76%) during the early phase but were uncommon during the late phase (29%). Total nasal obstruction occurred in 94% during the early phase. In contrast, unilateral nasal obstruction presented in 82% during the late phase, whereas total nasal obstruction was present only in 41%. The most common type of late phase nasal obstruction shown by PAR was alternating nasal obstruction.

Topics: Adolescent; Adult; Allergens; Blood Proteins; Case-Control Studies; Chymases; Eosinophil Granule Proteins; Female; Follow-Up Studies; Histamine; Humans; Inflammation Mediators; Inhalation; Leukotriene C4; Male; Middle Aged; Nasal Mucosa; Nasal Obstruction; Nasal Provocation Tests; Prostaglandin D2; Rhinitis, Allergic, Seasonal; Ribonucleases; Serine Endopeptidases; Sneezing; Tryptases

A quantitative determination of the inflammatory mediators was performed and correlated with complaints and the measurement of the inflammatory cells in nasal secretions of 18 seasonal allergic rhinitis patients (group 1) outside the pollen season and 40 symptomatic patients (group 2) with seasonal allergic rhinitis during the pollen season. Ten nonallergic subjects (group 3) were also studied as a normal control group. In group 1, 17 (94%) out of 18 patients had an immediate response of nasal symptoms accompanied by a significant increase of histamine, leukotriene C4 (LTC4), and tryptase 5 min after nasal allergen challenge (NAC). One hour later, a simultaneous increase was seen both in the percentage of the eosinophils and in the eosinophil cationic protein (ECP) concentration. The eosinophil count reached a peak 2 h after NAC with a duration of 8 h, while the highest ECP level was reached only after 24 h with no clear-cut plateau. In group 2, a high percentage of eosinophils was observed. Mostly one observed significantly (p < 0.01) higher concentrations of ECP, LTC4 and histamine but not of tryptase than the baseline values of group 1. The authors concluded that during the pollen season allergic rhinitis reflects mainly a chronic state of allergic inflammation of the nasal mucosa involving various inflammatory components induced by one or more episodes of early-phase type allergic reaction. Infiltration of eosinophils and consequently release of the various late-phase inflammatory mediators into the nasal secretions are certainly believed to be the predominant pathophysiologic condition in the patients.

Topics: Adolescent; Adult; Allergens; Blood Proteins; Chymases; Eosinophil Granule Proteins; Female; Histamine; Humans; Inflammation; Inflammation Mediators; Leukotriene C4; Male; Middle Aged; Nasal Mucosa; Nasal Provocation Tests; Rhinitis, Allergic, Seasonal; Ribonucleases; Serine Endopeptidases; Tryptases

It has been demonstrated that platelet-activating factor (PAF)-acether can induce nasal neutrophilia and eosinophilia, with a different degree of responsiveness in atopic and in nonatopic subjects. The aim of this study was to evaluate whether PAF can also induce the release of secondary mediators in the human nose. Ten patients with allergic rhinitis and 10 normal subjects underwent nasal challenge with PAF (500 nmol), lyso-PAF (500 nmol) and saline solution. Nasal lavages were performed before and after challenge to evaluate changes in nasal cytology and release of histamine, immunoreactive leukotriene (iLT) C4 and eosinophil cationic protein (ECP). PAF caused neutrophilia and eosinophilia, which appeared earlier in atopic than in nonatopic subjects (30 min vs 1 h), and peaked 3 h after challenge in both groups. Lyso-PAF caused mild neutrophilia, which appeared 3 h after challenge in both groups; an increase in eosinophil counts was observed 3 h after challenge in atopic subjects, but not in nonatopic subjects. PAF insufflation caused a significant release of ECP in nasal lavage fluids 30 min and 3 h after challenge in atopic subjects, and 3 h after challenge in nonatopic subjects. ECP levels in the nasal lavages collected 30 min and 3 h after challenge with PAF were higher in atopic than in nonatopic subjects. Eosinophil counts correlated with ECP levels in the nasal lavages collected 30 min after PAF challenge in atopic subjects. Nasal challenge with lyso-PAF did not provoke any release of ECP. No significant increase of histamine and iLTC4 levels in nasal lavages was found after challenge with either PAF or lyso-PAF.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Animals; Blood Proteins; Chick Embryo; Eosinophil Granule Proteins; Eosinophils; Female; Histamine Release; Humans; Leukocyte Count; Leukotriene C4; Male; Nasal Lavage Fluid; Nasal Mucosa; Nasal Provocation Tests; Neutrophils; Platelet Activating Factor; Rhinitis, Allergic, Seasonal; Ribonucleases

By using the microsuction technique, quantitative determination of the chemical mediators in nasal secretions was performed in 40 patients with seasonal allergic rhinitis during the pollen season. The aim of this study was to investigate the actual concentrations of these important mediators in nasal secretions during natural allergen exposure so as to better understand the pathophysiology of allergic rhinitis. The median concentrations of four mediators, were histamine: 51.5 ng/g (range: 4-146 ng/g); tryptase: 0 (range: 0-84 microU/g); leukotriene C4 (LTC4): 23 ng/g (range: 11-77 ng/g); and eosinophil cationic protein (ECP): 410 ng/g (range: 6-2380 ng/g). The authors compared these concentrations with those of the same mediator found in a previous study of seasonal allergic rhinitis patients after nasal challenge outside the pollen season. The present study demonstrates that during the season allergic rhinitis reflects a chronic state of allergic inflammation of the nasal mucosa involving various inflammatory mediators induced by one or more episodes of early type allergic reaction.

Topics: Adolescent; Adult; Allergens; Blood Proteins; Chymases; Eosinophil Granule Proteins; Female; Histamine; Humans; Inflammation Mediators; Leukotriene C4; Male; Manometry; Middle Aged; Nasal Mucosa; Nose; Rhinitis, Allergic, Seasonal; Ribonucleases; Serine Endopeptidases; Tryptases