leukotriene-c4 and Rhinitis--Allergic--Perennial

Bu-zhong-yi-qi-tang, an ancient formula of Chinese medicine usually used in the treatment of allergic diseases, was evaluated in the treatment of patients with perennial allergic rhinitis. In this study, 60 patients allergic to house dust mite allergen confirmed by skin test and MAST test were recruited and randomized. An experimental group of 36 patients was treated with Bu-zhong-yi-qi-tang, whereas a control group of 24 patients was treated with a non-effective formula Ping-wei-san for 3 months. The nasal symptomatic scores and the responses of polymorphonuclear neutrophils (PMN) to IL-4-stimulation were measured after treatment. The nasal symptomatic scores in the experimental group were significantly improved (3.78+/-0.09 before treatment vs. 0.57+/-0.06 after treatment). In contrast, no change was found in symptomatic scores in the control group (3.17+/-0.12 before treatment vs. 2.79+/-0.14 after treatment). Moreover, total serum IgE and the IL-4-stimulated production of PGE(2) and LTC(4) by PMN was significantly suppressed in the experimental group after treatment compared to the control group. The COX-2 mRNA expression in IL-4-stimulated PMN was also significantly suppressed after Bu-zhong-yi-qi-tang treatment. These results suggest that Bu-zhong-yi-qi-tang but not Ping-wei-san was beneficial to the patients with perennial allergic rhinitis via suppressed nasal inflammation by an antiinflammatory effect.

Topics: Adolescent; Adult; Anti-Inflammatory Agents; Cyclooxygenase 2; Dinoprostone; Drugs, Chinese Herbal; Female; Gene Expression Regulation, Enzymologic; Humans; Immunoglobulin E; Interleukin-4; Leukotriene C4; Male; Neutrophils; Rhinitis, Allergic, Perennial; RNA, Messenger

Interferon gamma (IFN-gamma) is a cytokine characterized by different biologic and immunologic activities. Leukotrienes are proinflammatory mediators released both in immediate and late allergic reactions. These facts suggest that leukotrienes and IFN-gamma might cooperate in allergic inflammation. The aim of this study was to investigate the influence of IFN-gamma on leukotriene C4 (LTC4) production by peripheral blood leukocytes isolated from the patients suffering from perennial allergic rhinitis caused by allergy to mites. Eleven patients entered the study. LTC4 released from leukocytes stimulated by Dermatophagoides pteronyssinus allergen alone, and after preincubation with IL-3 was examined. The influence of preincubation of leukocytes with IFN-gamma in concentrations of 1,10 and 100 ng/ml on mentioned allergen stimulation procedures was also investigated. The concentration of LTC4 in supernatants was measured by CAST-ELISA method. The difference between concentration of LTC4 released in medium with and without IL-3 represented the effect of priming. We observed that IFN-gamma suppressed release of LTC4 only from leukocytes incubated with IL-3 in dose-dependent fashion. On the basis of these data we can postulate that IFN-gamma inhibits IL-3 dependent cell priming, but has no influence on LTC4 secretion per se.

Topics: Adult; Allergens; Animals; Chronic Disease; Dermatophagoides pteronyssinus; Enzyme-Linked Immunosorbent Assay; Female; Humans; Immunoglobulin E; In Vitro Techniques; Interferon-gamma; Interleukin-3; Leukocytes; Leukotriene C4; Male; Rhinitis, Allergic, Perennial; Time Factors

In our previous study, we found a new mixed formula of Chinese herbs containing Shin-yi-san + Xiao-qing-long-tang + Xiang-sha-liu-jun-zi-tang (9 + 3 + 3 g divided in three doses/day) was beneficial to the patients with perennial allergic rhinitis (AR) via complicated immunomodulatory effects on both mononuclear cells (MNC) and polymorphonuclear neutrophils (PMN). In the present study, we further determined the effects of nasal fluid from AR patients on the functions of human PMN before and after treatment with the mixed formula. We found the nasal discharge, but not serum, from AR group with high serum IgE (H-IgE, serum IgE >200 KIU/l) before treatment exerted many stimulating effects on normal PMN including delayed apoptosis, enhanced production of soluble intercellular adhesion molecule 1 (sICAM-1), interleukin 8 (IL-8) and prostaglandin E2 (PGE2), increased phagocytosis, and augmented cyclooxygenase 2 (COX-2) mRNA expression of PMN. However, these stimulating effects of nasal fluid on PMN were not found in low IgE group (L-IgE, serum IgE <200 KIU/l). These PMN-enhancing effects of H-IgE nasal fluid were abolished after 3-month treatment with the mixed Chinese herb formula. In conclusion, our results suggest that the new mixed herb formula treatment suppressed nasal mucosa inflammation by normalizing stimulatory effects of allergic nasal discharge of patients with H-IgE allergic rhinitis.

Topics: Adolescent; Adult; Apoptosis; Cells, Cultured; Culture Media, Conditioned; Cyclooxygenase 2; Dinoprostone; Drugs, Chinese Herbal; Female; Humans; Immunoglobulin E; Inflammation; Intercellular Adhesion Molecule-1; Interleukin-8; Isoenzymes; Leukotriene C4; Male; Membrane Proteins; Mucus; Nasal Mucosa; Neutrophils; Phagocytosis; Prostaglandin-Endoperoxide Synthases; Rhinitis, Allergic, Perennial; RNA, Messenger; Time Factors

KOB03 is a polyherbal medicine derived from an oriental prescription traditionally used to treat allergic diseases. In the present study, we compared the efficacy of KOB03 with modern drugs such as ketotifen and montelukast in an experimental mouse model of allergic rhinitis (AR). Ketotifen is a H1 receptor antagonist and montelukast is a leukotriene receptor antagonist. Mice were treated with KOB03, ketotifen or montelukast in an established AR mouse model using ovalbumin (OVA)-sensitized/challenged BALB/c mice. The treatment of KOB03 had inhibitory effects on symptom scores, serum levels of OVA-specific IgE, histamine, leukotriene C4, IL-4, TNF-α, and IL-1β in AR mice, and the histolopathological changes of nasal mucosa with mucin release and inflammation. AR mice treated with KOB03 had significantly lower serum levels of OVA-specific IgE, LTC4, IL-4, and IL-1β than mice treated with ketotifen, whereas they only had significantly lower serum levels of OVA-specific IgE and IL-4 than those treated with montelukast. In addition, the histolopathological changes of nasal mucosa with eosinophil infiltration were significantly lower in the KOB03-treated mice than those in the ketotifen and montelukast-treated group. These results suggest that KOB03 has therapeutic potential for treating AR like other modern medicines.

Topics: Acetates; Animals; Anti-Allergic Agents; Antigens; Cyclopropanes; Cytokines; Disease Models, Animal; Histamine H1 Antagonists; Immunoglobulin E; Ketotifen; Leukotriene Antagonists; Leukotriene C4; Male; Mice; Mice, Inbred BALB C; Nasal Mucosa; Ovalbumin; Plant Extracts; Quinolines; Rhinitis, Allergic; Rhinitis, Allergic, Perennial; Sulfides

Although CD23-dependent transcytosis of IgE and IgE-derived immune complexes across respiratory epithelial cells is likely to play a pivotal role in the initiation and development of airway allergic inflammation, there is currently a lack of physiological support for this phenomena to suggest that the targeting of CD23 could be used as a means of therapeutic intervention. The present study was designed to detect the CD23 expression in the nasal mucosa of allergic rhinitis (AR) murine model by immunohistochemistry and western blotting, and to investigate whether intranasal anti-CD23 treatment could inhibit allergen-induced upper airway inflammation in the AR model. This is the first report to show that CD23 was constitutively expressed in murine nasal epithelial cells, and its expression was significantly up-regulated in the AR murine model. In vivo, the up-regulation of CD23 expression was correlated with increased serum IL-4 levels. Following intranasal anti-CD23 treatment, nasal symptoms were alleviated and histopathologic examination showed a significant decrease in eosinophilic infiltration. Meanwhile, ELISA analysis showed levels of serum leukotriene C4 (LTC4), eosinophil cation protein (ECP), ovalbumin (OVA)-specific IgE and IL-4 also significantly decreased, as were LTC4 and OVA-specific IgE in the nasal lavage fluid. Furthermore, Western blotting analysis showed that ECP expression in the nasal mucosa was down-regulated. Finally, flow cytometric analysis revealed anti-CD23 treatment inhibited Th2 cell responses. These results indicate that intranasal anti-CD23 treatment can reduce allergic responses in a murine model of allergic rhinitis.

Topics: Administration, Intranasal; Allergens; Animals; Budesonide; Disease Models, Animal; Down-Regulation; Eosinophil Cationic Protein; Eosinophils; Epithelial Cells; Female; Hypersensitivity; Immunoglobulin E; Inflammation; Interleukin-4; Leukotriene C4; Mice; Mice, Inbred BALB C; Nasal Mucosa; Ovalbumin; Random Allocation; Receptors, IgE; Rhinitis, Allergic; Rhinitis, Allergic, Perennial; Th2 Cells; Up-Regulation

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

The house dust mite Blomia tropicalis (B. tropicalis) was found to be the most prevalent domestic mite in Singapore. However, its pathogenicity in allergic airway diseases remains to be investigated.. Twenty adults with persistent allergic rhinitis (PAR) were studied. Five had a history of asthma, and all were asymptomatic except one who was under treatment with low-dose inhaled corticosteroid. Nasal challenge was carried out by nasal spray with phosphate-buffered saline (PBS) and with increasing concentrations of crude B. tropicalis extracts (0.6, 6.0 and 60 micro g/ml) at 15 min intervals. Subjective symptom scores and absolute number of sneezes were recorded together with objective measurements of spirometry (forced expiratory volume in 1 s, FEV1) and acoustic rhinomanometry (volume of the nasal cavity). These were performed at baseline, 5 min after each incremental challenge, and 30 min, 1 h, 3 h, 5 h and 7 h after the last challenge. Meanwhile, concentrations of mediators in nasal secretions (tryptase, leukotriene C4 (LTC4) and eosinophil cationic protein (ECP)) were measured in nasal aspirate samples at similar time intervals. An identical (control) challenge procedure with PBS alone was repeated in seven patients after a washout period of at least 2 weeks.. Significant increases in the subjective and objective nasal symptoms, together with a significant increase of tryptase and LTC4 concentrations in nasal secretion, were found 5 min after each challenge with B. tropicalis, but not with PBS. There was no definitive pattern of the late-phase nasal response in either subjective symptoms or objective measurements. Three patients (3/5) with a history of asthma showed a fall in FEV1 readings (33%, 22% and 11% from baseline, respectively) at 7 h post challenge with concomitant mild wheezing in the night.. Our study demonstrates direct evidence of allergic nasal response to B. tropicalis in sensitized adults. It shows that nasal provocation may also provoke concomitant asthmatic symptoms during the late-phase reaction, especially in people with a history of asthma.

Topics: Adult; Allergens; Animals; Blood Proteins; Cross Reactions; Dust; Eosinophil Granule Proteins; Eosinophils; Female; Forced Expiratory Volume; Humans; Leukotriene C4; Male; Mites; Nasal Mucosa; Nasal Provocation Tests; Rhinitis, Allergic, Perennial; Ribonucleases; Serine Endopeptidases; Sodium Chloride; Time Factors; Tryptases

Topics: Aspirin; Drug Hypersensitivity; Enzyme-Linked Immunosorbent Assay; Humans; Leukocytes; Leukotriene C4; Leukotriene D4; Leukotriene E4; Rhinitis, Allergic, Perennial; Sensitivity and Specificity; Sinusitis

Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) are members of the immunoglobulin superfamily adhesion molecules on vascular endothelium and important in the development of eosinophil (EOS) accumulation in allergic inflammation. To define the role of these adhesion proteins in EOS inflammation, peripheral blood EOS from allergic donors were incubated in either buffer (control)-, recombinant human (rh)-VCAM-1-, or rh-ICAM-1-coated plates, and the effects of these adhesion proteins on EOS effector functions were determined. VCAM-1 induced spontaneous EOS adhesion whereas EOS adhesion to ICAM-1 required a second signal, such as granulocyte macrophage colony-stimulating factor (GM-CSF). Although only VCAM-1 stimulated EOS superoxide anion (O2-) generation, the addition of GM-CSF (100 pM) to the reactions resulted in a greater and equivalent production of O2- with VCAM-1 and ICAM-1. In the presence of GM-CSF, ICAM-1 and VCAM-1 caused significant release of EOS-derived neurotoxin (EDN). Moreover, only ICAM-1 (no GM-CSF) promoted calcium ionophore A23187 (0.2 microM)-induced EOS leukotriene C4 (LTC4). Enhanced O2- generation, EDN release, and LTC4 generation observed with ICAM-1 and VCAM-1 were significantly inhibited by anti-beta2-integrin antibody. These results suggest that ICAM-1 and VCAM-1 are important in determining the eventual function of airway EOS.

Topics: Adult; Antibodies; Antigens, CD; Asthma; CD18 Antigens; Cell Adhesion; Eosinophil-Derived Neurotoxin; Eosinophils; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Integrin alpha4; Intercellular Adhesion Molecule-1; Leukotriene C4; Middle Aged; Proteins; Recombinant Proteins; Rhinitis, Allergic, Perennial; Ribonucleases; Superoxides; Vascular Cell Adhesion Molecule-1

To examine whether cysteinyl leukotrienes (cysLTs: LTC4, LTD4 and LTE4) induce symptoms of allergic rhinitis via their receptors, we studied the following: i) the specific binding of radiolabeled cysLTs to guinea pig nasal mucosa membrane and ii) effects of nasal LTD4 challenge in normal guinea pigs. The binding study indicated that there was a single population of binding sites for LTC4, LTD4 and LTE4 with Kd and Bmax values of 34.9+/-2.0, 0.252+/-0.015 and 0.589+/-0.039 nM and 10, 140+/-490, 122+/-11 and 306+/-23 fmol/mg protein, respectively. The in vivo study showed that topical nasal challenge of LTD4 (0.1-30 microg/nose) increased nasal secretion, nasal airway resistance and nasal eosinophil infiltration without inducing sneezing. While the increases in nasal secretion and nasal airway resistance were transient, peaking 10 to 20 min after LTD4 challenge, nasal eosinophil infiltration persisted at least until 24 hr post-challenge. These nasal symptoms were dose-dependently suppressed by oral administrations of pranlukast (0.3-3 mg/kg). The results suggest that cysLTs cause not only early-phase symptoms but also nasal eosinophil migration, a characteristic associated with the late-phase symptom of allergic rhinitis, via a receptor-mediated mechanism. Cysteinyl leukotrienes, thus, may be important mediators in allergic rhinitis.

Topics: Administration, Oral; Airway Resistance; Animals; Anti-Asthmatic Agents; Binding Sites; Chromones; Dose-Response Relationship, Drug; Eosinophils; Guinea Pigs; In Vitro Techniques; Leukotriene Antagonists; Leukotriene C4; Leukotriene D4; Leukotriene E4; Male; Nasal Mucosa; Receptors, Leukotriene; Rhinitis, Allergic, Perennial; Tritium

We examined the biological characteristics of normodense and hypodense eosinophils prepared from the peripheral blood of the patients with allergic rhinitis caused by house dust mites by measuring leukotriene C4 (LTC4), platelet-activating factor (PAF), and superoxide anions. The normodense (density: 1.100-1.095) and the hypodense (density: 1.080-1.070) eosinophils were prepared by a Percoll density gradient. The normodense eosinophils produced a greater amount of LTC4 (15 ng/10(6) cells) after stimulation by calcium ionophore A23187 than the hypodense eosinophils (1.8 ng/10(6) cells). On the other hand, in the hypodense eosinophils higher amounts of both PAF (5210 pg/10(7) cells/15 min) and superoxide anions (0.33 nmoles/10(7) cells/min) were produced by calcium ionophore A23187 than in the normodense eosinophils, 501 pg/10(7) cells/15 min and 0.18 nmoles/10(7) cells/min, respectively. Considering these results, it is suggested that the two eosinophil subpopulations have distinct biological roles in generating these inflammatory mediators which appear as typical pathological features of allergic rhinitis.

Topics: Allergens; Animals; Calcimycin; Cell Separation; Dust; Eosinophils; Humans; Inflammation Mediators; Ionophores; Leukotriene C4; Mites; Platelet Activating Factor; Rhinitis, Allergic, Perennial; Specific Gravity; Superoxides

To determine whether nasal allergic symptoms can cause bronchial hyperresponsiveness to methacholine, 30 subjects with allergic rhinitis (22 with allergic rhinitis and 8 with allergic asthmatic rhinitis) were studied. All subjects were skin test positive to Dermatophagoides pteronyssinus (DP) and underwent nasal allergic provocation with DP. After provocation, there was a severe nasal allergic reaction in the challenged nostril with a significant increase in nasal resistance both immediately and long (7 h) after DP exposure. There were no significant changes in the forced expiratory volume in 1 s and the forced expiratory flow rate between 25 and 75% of the forced vital capacity and in both allergic rhinitis and allergic asthmatic rhinitis patients. There was also no change in bronchial hyperresponsiveness to methacholine. The eosinophil counts, leukotriene B4, leukotriene C4 and platelet-activating factor levels in nasal discharges also showed no differences in both groups of patients. Our studies suggest that nasal provocation with limited allergen is a safe diagnostic technique. However, the relationship between nasal resistance and airway hyperreactivity is not obvious in this study. The similar concentrations of nasal inflammatory mediators in both allergic rhinitis and allergic asthmatic rhinitis indicate that bronchial hyperreactivity is not solely due to nasal drainage of inflammatory mediators.

Topics: Adolescent; Adult; Allergens; Antigens, Dermatophagoides; Bronchial Hyperreactivity; Eosinophils; Female; Glycoproteins; Humans; Leukocyte Count; Leukotriene B4; Leukotriene C4; Male; Methacholine Chloride; Nasal Mucosa; Nasal Provocation Tests; Platelet Activating Factor; Rhinitis, Allergic, Perennial