ovalbumin and Sneezing

Allergic rhinitis (AR) is one of the most common inflammatory diseases. IgE, inflammatory cytokine production and Th17/Tregs imbalance have been implicated in AR pathogenesis. Bufotalin, a component extracted from toad venom skin secretions and auricular glands, has anti-inflammatory activity and regulates Th17/Tregs balance. Here, the effects of bufotalin on AR were explored.. The AR mice model was established using ovalbumin (OVA). AR mice were treated with bufotalin started on Day 22 with various doses (1, 10, 100 μg or 1 mg per mouse) every day to Day 30. The sneezing and rubbing frequencies were counted. Serum levels of IL-1β, IL-10 and OVA-specific IgE were measured. The superficial cervical lymph nodes were harvested and the percentage of Tregs in lymph node was determined using CD4 and Foxp3 markers.. OVA treatment successfully induced AR model in mice with significantly increased sneezing and rubbing frequency, elevated levels of serum histamine, IL-1β, IL-10 and OVA-specific IgE. Bufotalin treatment significantly ameliorated AR symptoms, with reduced histamine, IgE and IL-1β levels, as well as sneezing and rubbing frequency. Moreover, bufotalin treatment decreased the serum levels of IL-1β, IL-10 and OVA-specific IgE in AR mice.. Bufotalin ameliorated allergic rhinitis symptoms in AR mice by restoring Tregs in lymph node.

Topics: Animals; Cytokines; Disease Models, Animal; Histamine; Immunoglobulin E; Interleukin-10; Mice; Mice, Inbred BALB C; Nasal Mucosa; Ovalbumin; Rhinitis, Allergic; Sneezing

Inotodiol has been proven to have antitumor, antiviral, anti-inflammatory, and antiallergic properties. This study investigated the immunomodulatory capability of inotodiol in allergic rhinitis (AR) mice.. Forty BALB/c mice were divided into four groups, 10 mice each: control (CON), AR with phosphate-buffered saline (PBS) treatment (AR), inotodiol treatment (AR+Ino), and dexamethasone treatment (AR+Dex). Episodes of sneezing and nose rubbing were counted. Cytokines in nasal lavage fluid (NLF) and immunoglobulin in blood serum were measured. Nasal mucosae from each group were used for protein, reverse transcriptase-polymerase chain reaction (RT-PCR), and histological analyses. Splenocytes were cultured for evaluation of cytokine production in each group.. Symptoms of rubbing and sneezing improved in the group of AR+Ino and AR+Dex than in the AR. NLF in the AR+Ino and AR+Dex also showed a significant decrease in interleukin (IL)-5, IL-10, and IL-13 compared to the AR. In addition, the number of eosinophils, goblet cells, and mast cells were notably lower in the nasal mucosae of the AR+Ino and AR+Dex. IL-4 and IL-17A in the AR+Ino and AR+Dex groups were decreased compared to the AR. Chemokines related to mast cell degradation were also decreased in the AR+Ino and AR+Dex groups. Total immunoglobulin (Ig)E, specific IgE and ovalbumin (OVA)-specific IgG1, and histamine levels were also significantly lower in the AR+Ino and AR+Dex groups. IL-10 and IL-13 were notably increased in the splenocytes of the AR after OVA stimulation, whereas the other groups showed no change.. These results indicate inotodiol can help suppress allergic responses by immunomodulation activities.

Topics: Animals; Cytokines; Disease Models, Animal; Immunoglobulin E; Inflammation; Interleukin-10; Interleukin-13; Mice; Mice, Inbred BALB C; Nasal Mucosa; Ovalbumin; Rhinitis, Allergic; Sneezing

The pathogenesis of allergic rhinitis (AR) is ambiguous, while it is clear that various immune cells and cytokines play crucial roles in its occurrence and development.. To investigate the effect of exogenous interleukin-10 (IL-10) on the expression of fibrinogen (FIB), procalcitonin (PCT), hypersensitive C-reactive protein (hs-CRP), and Th17/Treg-IL10/IL-17 axis balance in the nasal mucosa of rats with AR.. In this study, 48 female-specific pathogen-free Sprague-Dawley rats were randomly divided into 3 groups: blank control group, AR group, and IL-10 intervention group. The AR model was established in the AR group and IL-10 group. The rats in the control group were treated with normal saline; the rats in the AR group were given 20 μL of saline containing 50 μg of ovalbumin (OVA) every day. The rats in the IL-10 intervention group were intraperitoneally injected with 1 mL of 40 pg/kg IL-10 and provided with OVA. The IL-10 intervention group was composed of mice with AR that received IL-10. The behavior of nasal allergic symptoms (such as nasal itching, sneezing, and runny nose) and the hematoxylin and eosin staining of nasal mucosa were observed. The levels of FIB, PCT, hs-CRP, IgE, and OVA sIgE in serum were determined by enzyme-linked immunosorbent assay. The levels of Treg and Th17 cells in serum were detected by flow cytometry. The protein levels of TGF-β, IL-10, and IL-17 in nasal mucosa were detected by the Western-blot method.. The scores of snots, nasal itching, and sneezing in the AR group were significantly higher than those in the control group, while the scores of the above symptoms in the IL-10 intervention group were lower than those in the AR group. The levels of FIB, PCT, hs-CRP, IgE, and OVA sIgE in serum and the protein levels of IL-10 and IL-17 in the nasal mucosa in the AR group were higher than those in the blank control group. Meanwhile, the levels of FIB, PCT, hs-CRP, IgE, and OVA sIgE in serum and IL-10 and IL-17 protein in the nasal mucosa in the IL-10 group were lower than those in the AR group.. IL-10 can relieve the allergy of AR rats by affecting the expression of FIB, PCT, and hs-CRP, as well as the balance of the Th17/Treg-IL10/IL-17 axis in the nasal mucosa of AR rats.

Topics: Animals; C-Reactive Protein; Disease Models, Animal; Female; Fibrinogen; Hemostatics; Immunoglobulin E; Interleukin-10; Interleukin-17; Mice; Mice, Inbred BALB C; Nasal Mucosa; Ovalbumin; Procalcitonin; Pruritus; Rats; Rats, Sprague-Dawley; Rhinitis, Allergic; Sneezing; T-Lymphocytes, Regulatory; Th17 Cells

Luteolin (LO) has been reported to be a potential drug for allergic rhinitis (AR). This paper explored the mechanism of LO in AR.. The nasal sneezing frequency, nasal mucosa thickness, and levels of anti-OVA-IgE, Beclin1, LC3II/LC3I, IL-17A as well as RORγt were enhanced whereas anti-OVA-IgG2a, IL-10, and Foxp3 levels were inhibited in a mouse model of OVA-induced AR, which were reversed by LO or 3-MA treatment.. LO restored Treg/Th17 balance to ameliorate AR in a mouse model.

Topics: Animals; Beclin-1; Disease Models, Animal; Forkhead Transcription Factors; Immunoglobulin E; Immunoglobulin G; Interleukin-10; Luteolin; Mice; Mice, Inbred BALB C; Nuclear Receptor Subfamily 1, Group F, Member 3; Ovalbumin; Rhinitis, Allergic; Sneezing; T-Lymphocytes, Regulatory; Th17 Cells

Allergic reaction is the most common nasal conditions worldwide and it will remain throughout life. The symptoms of an allergic reaction include sneezing, itching, hives, swelling, difficulty breathing, and a runny nose. Hydroxysafflor yellow A (HYA) is a flavonoid compound which is the active phyto-constituent of flower of Carthamus tinctorius L., and exhibited the various medicinal activities like antioxidant, anti-inflammatory and cardiovascular protective effects. This study aimed to assess the efficacy and mode of action of HYA against the allergic rhinitis induced by ovalbumin in mice. HYA was given orally to the Swiss BALB/s mice once daily, 1 h before, they were challenged with ovalbumin (OVA) via intranasal administration, after that the mice were sensitized via intraperitoneal injection of OVA. Allergic nasal symptoms, body weight, spleen weight, OVA-specific immunoglobulins, inflammatory cytokines, Th17 cytokines and Th17 transcription factors also estimated. HYA had a significant (p < .001) effect on body weight and reduced spleen weight. It effectively decreased the nasal symptoms of allergy such as sneezing, rubbing, and redness. HYA significantly reduced the level of malonaldehyde (MDA) and improved levels of superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) and glutathione (GSH). It also remarkably decreased the levels of Th2 cytokines and Th17 transcription factors like RAR-related orphan receptor gamma (ROR-γ), signal transducer and activator of transcription 3 (STAT3) and phosphor signal transducer and activator of transcription 3 (p-STAT3), while increasing levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). The treatment with HYA improved the lung histology in mice with allergic rhinitis. The results suggest that HYA may have therapeutic potential against ovalbumin-induced allergic rhinitis in mice, by altering the Th17/Treg balance and improving the Nrf2/HO-1 signaling pathway.

Topics: Animals; Body Weight; Cytokines; Disease Models, Animal; Heme Oxygenase-1; Mice; Mice, Inbred BALB C; Nasal Mucosa; NF-E2-Related Factor 2; Ovalbumin; Rhinitis, Allergic; Signal Transduction; Sneezing; STAT3 Transcription Factor

Neurokinin-1 receptor (NK-1R) and normal T cell expressed and secreted (RANTES) have been shown to play important roles in allergic rhinitis (AR). However, whether the regulating effect of NK-1R in AR is achieved via RANTES remains unknown.. In the present study, Sprague-Dawley rats were sensitized and challenged with ovalbumin to make AR models. During the challenge period, the rats were treated intranasally with NK-1R-specific small interfering RNA (siRNA) for NKR group, negative siRNA for NCS group, rats in NSAR group and NS group were given saline. The amount of nasal secretion and the numbers of nose rubs and sneezes were measured in each rat. The levels of NK-1R and RANTES in the nasal mucosal tissues were determined through real-time fluorescence quantitative RT-PCR and immunohistochemical staining. The numbers of eosinophils in the collected nasal lavage fluid (NLF) were counted, and the concentration of RANTES in NLF was determined by enzyme-linked immunosorbent assay.. Compared with that in the NS group, the expression of NK-1R and RANTES was significantly higher in the nasal mucosa of NSAR and NCS group rats. The sneezing and nose rubbing counts and the amount of nasal secretions were increased significantly in the NSAR and NCS groups. Rats in the NKR group experienced greater relief from AR symptoms than rats in the NSAR and NCS groups. Furthermore, knockdown of NK-1R expression also significantly eliminated RANTES expression and eosinophil infiltration in the nasal mucosa of NKR group rats.. For the first time, we show that intranasal treatment with NK-1R-specific siRNA can significantly decrease RANTES expression, AR-related symptoms, and eosinophil inflammation, suggesting that the regulating effect of NK-1R in the development of AR occurs via alteration of RANTES expression.

Topics: Animals; Chemokine CCL5; Disease Models, Animal; Gene Knockdown Techniques; Nasal Mucosa; Ovalbumin; Rats; Rats, Sprague-Dawley; Receptors, Neurokinin-1; Rhinitis, Allergic; RNA, Small Interfering; Sneezing

Allergic rhinitis (AR) is regarded as a prevalent and non-infectious inflammation in nasal mucosa, and astragalus polysaccharide (APS) could mitigate inflammation.. Herein, this study probed the specific mechanism of APS in inflammatory responses in AR.. APS reduced Treg/Th17 imbalance via suppressing NF-kB expression, thereby ameliorating inflammatory responses in AR.

Topics: Animals; Disease Models, Animal; Forkhead Transcription Factors; Guinea Pigs; Immunoglobulin E; Inflammation; Interleukin-6; Mice; Mice, Inbred BALB C; Nasal Mucosa; NF-kappa B; Ovalbumin; Polysaccharides; Rhinitis, Allergic; Sneezing; T-Lymphocytes, Regulatory; Th17 Cells; Transforming Growth Factor beta

Allergic rhinitis (AR) is an allergic disease induced by the T helper 2 (TH2) lymphocyte immune response, where its mediators are the primary cause of clinical symptoms. Environmental factors are the primary determinants of the allergic response in genetically susceptible individuals. This study investigates the effects of climate conditions (warm, cold, humid, and dry) on allergic rhinitis. AR models were created in mice under 4 different conditions. We investigated AR-related behavior (sneezing and nose rubbing), as well as total immunoglobulin E (IgE), histamine, interleukin-4 (IL-4), leukotriene (LT) B4 and LTC4 levels, and gene expression of CysLT1R, HRH1, and MUC5a. Nose rubbing, histamine levels, and the expression of MUC5a and HRH1 were increased in AR models in cold conditions, and sneezing was increased in AR models kept in dry conditions. LTB4 and LTC4 levels and the expression of CysLT1R in AR models kept in a wet environment also significantly increased compared with the control group. The levels of total IgE and IL-4 showed no significant changes. Air temperature and humidity affect AR pathophysiology, and weather conditions can be essential in controlling AR.

Topics: Animals; Disease Models, Animal; Histamine; Humidity; Immunoglobulin E; Interleukin-4; Leukotriene C4; Mice; Mice, Inbred BALB C; Nasal Mucosa; Ovalbumin; Rhinitis, Allergic; Sneezing; Temperature

To explore the regulatory effects of microRNA (miRNA)-224 and its potential target gene, cyclin dependent kinase 9 (CDK9), in the pathological process of allergic rhinitis (AR).. To investigate the role of miR-224 and CDK9, it was screened by bioinformatics prediction software and verified by dual-luciferase reporter assay. The mouse model of AR was established by ovalbumin (OVA).The animal models were intervened with miR-224 agomir, negative control agomir, and saline respectively. The symptoms of sneezing and nasal rubbing were recorded. The expressions of miR224, CDK9, and cytokines in the nasal mucosa of different groups were analyzed by rt-PCR or western blotting. Enzyme-linked immunoassay (ELISA) was used to evaluate the levels of IgE and Histamine (HA) in the serum. The infiltration of inflammatory cells in the nasal mucosa was studied by immunohistochemistry. The expression and distribution of CDK9 in the nasal mucosa of mice were revealed by immunofluorescence.. In the nasal mucosa of the animal models, the level of miR-224 was downregulated, while that of CDK9 was upregulated. The upregulation of miR-224 by miR-224 agomir reduced the frequencies of nasal rubbing and sneezing, the expression of CDK9, the levels of cytokines, and the concentrations of IgE and HA. Moreover, miR-224 appeared to attenuate the infiltration of inflammatory cells and hypersecretion of glands in the nasal mucosa. The expression of CDK9, which was distributed under the mucosa, especially in the submucosa interstitial tissue, was significantly reduced.. MiR-224 affected the pathogenesis of AR by targeting CDK9. It proves that miR-224 could be a novel potential therapeutic target for AR.

Topics: Animals; Cyclin-Dependent Kinase 9; Cytokines; Disease Models, Animal; Histamine; Immunoglobulin E; Inflammation; Mice; Mice, Inbred BALB C; MicroRNAs; Nasal Mucosa; Ovalbumin; Rhinitis, Allergic; Sneezing

Th2 immune cells infiltration into nasal mucosa is one of the characters of allergic rhinitis (AR). We aimed to explore whether inhibition of Th2 immune cells infiltration would attenuate AR progression. AR mouse model was established by i.p. injection of ovalbumin (OVA). The infiltrated immune cells into nasal lavage fluid were detected by flow cytometry. Cytokine concentration in serum was determined by ELISA. AR mice symptoms were indicated by the number of sneezing and nasal rubbing events. In AR mice, CCL2 expression levels and CD45

Topics: Animals; Chemokine CCL2; Disease Models, Animal; Mice; Mice, Inbred BALB C; Monocytes; Nanomedicine; Nanoparticles; Nasal Mucosa; Ovalbumin; Rhinitis, Allergic; RNA, Small Interfering; Sneezing; Th2 Cells

CARAS is an airway inflammation of allergic individuals, with a type 2 immune response. The pharmacotherapy is based on drugs with relevant side effects. Thus, the goal of this study evaluated the alkaloids warifteine (War) and methylwarifteine (Mwar) from Cissampelos sympodialis in CARAS experimental model. Therefore, BALB/c mice were ovalbumin (OVA) sensitized and challenged and treated with both alkaloids. Treated animals showed a decrease (p < 0.05) of allergic signs as sneezing and nasal rubbings, histamine nasal hyperreactivity, and inflammatory cell migration into the nasal (NALF) and the bronchoalveolar (BALF) fluids, main eosinophils. In the systemic context, only Mwar reduced eosinophilia, however, both alkaloids reduced the serum levels of OVA-specific IgE. Histological analysis revealed that the alkaloids decreased the inflammatory cells into the subepithelial and perivascular regions of nasal tissue and the peribronchiolar and perivascular regions of lung tissue. Hyperplasia/hypertrophy of nasal and lung goblet cells were reduced in alkaloid treated animals; however, the treatment did not change the number of mast cells. The lung hyperactivity was attenuated by reducing hyperplasia of fibroblast and collagen fiber deposition and hypertrophy of the lung smooth muscle layer. The immunomodulatory effect was by decreasing of type 2 and 3 cytokines (IL-4/IL-13/IL-5 and IL-17A) dependent by the increasing of type 1 cytokine (IFN-γ) into the BALF of treated sick animals. Indeed, both alkaloids reduced the NF-кB (p65) activation on granulocytes and lymphocytes, indicating that the alkaloids shut down the intracellular transduction signals underlie the transcription of T

Topics: Alkaloids; Animals; Anti-Allergic Agents; Asthma; Behavior, Animal; Bronchoalveolar Lavage Fluid; Cissampelos; Collagen; Cytokines; Disease Models, Animal; Eosinophils; Female; Immunoglobulin E; Inflammation; Lung; Mast Cells; Mice, Inbred BALB C; Mucus; Nasal Lavage Fluid; Nasal Mucosa; Ovalbumin; Rhinitis, Allergic; Signal Transduction; Sneezing; Transcription Factor RelA

Currently, a variety of studies have demonstrated that green tea has anti-allergic properties, and the major polyphenolic compound, epigallocatechin gallate (EGCG), plays a significant role. Some research indicates that EGCG reduces the production and expression of allergy-related substances. Therefore, EGCG has a potential effect of reducing allergic rhinitis (AR). In this study, the effect of EGCG on allergic rhinitis in an ovalbumin (OVA)-induced mouse model was investigated. After administration of EGCG, the number of sneezes and the occurrence of nasal rubbing were significantly decreased, the concentrations of immunoglobulin E (IgE) and histamine were suppressed in AR mouse serum, the levels of interleukin (IL)-1β, IL-4, and IL-6 were reduced in AR mice nasal lavage fluid (NLF), and the nasal mucosa mRNA and protein expression of cyclooxygenase 2 (COX-2), IL-1β, IL-4, and IL-6 were inhibited. The data indicate that EGCG has a beneficial effect of reducing allergic rhinitis.

Topics: Allergens; Animals; Anti-Inflammatory Agents; Catechin; Cyclooxygenase 2; Cytokines; Disease Models, Animal; Female; Histamine; Humans; Immunoglobulin E; Inflammation Mediators; Mice; Mice, Inbred BALB C; Ovalbumin; Rhinitis, Allergic; Sneezing; Tea

Prostaglandin D2(PGD2) is involved in the pathogenesis of allergic rhinitis. However, the sensory nervous system-mediated contributions of PGD2to the symptoms of allergic rhinitis remain unclear. We investigated the involvement of PGD2in these symptoms and in neuronal excitation by in vivo and ex vivo experiments. In an ovalbumin-induced model of allergic rhinitis in guinea pigs, the number of sneezing, nasal rubbing, and nasal secretion events were assessed after the nasal cavity instillation of PGD2, histamine, or a combination of PGD2and histamine. In situ hybridization for PGD2receptor 1 (DP1) mRNA transcripts and immunohistochemical analysis of histamine H1receptor protein expression in guinea pig trigeminal ganglion (TRG) were performed. The effects of DP1receptor activation on the excitability of TRG neurons to electrical and histamine stimuli were assessed using whole-cell patch-clamp recordings. Histamine induced more sneezing, nasal rubbing, and nasal secretion events than PGD2 PGD2augmented histamine-induced responses, whereas pretreatment with a DP1receptor-selective antagonist completely suppressed PGD2-induced augmentation. DP1receptor mRNA transcripts and H1receptor protein expression could be detected in TRG neurons. Moreover, a DP1receptor agonist caused significant increases in the number of histamine-induced action potentials and depolarization, and reduced the current threshold in small-diameter neurons. Our findings show that PGD2-DP1receptor signaling augments the symptoms of allergic rhinitis via the sensory nervous system by modulating nasal neuronal activation to various stimuli, such as histamine. These findings suggest that DP1receptor antagonist has therapeutic potential for the treatment of allergic rhinitis.

Topics: Action Potentials; Animals; Behavior, Animal; Electric Stimulation; Guinea Pigs; Histamine; Male; Neurons; Ovalbumin; Patch-Clamp Techniques; Prostaglandin D2; Receptors, Immunologic; Receptors, Prostaglandin; Rhinitis, Allergic; Sneezing; Trigeminal Ganglion

To establish the murine models of local allergic rhinitis (LAR) and allergic rhinitis (AR) by using ovalbumin (OVA), and to investigate the relationship between them.. Thirty BALB/c mice were divided into 5 groups, (1) the nasally sensitized group (group A1) that was challenged with OVA by a 10 d procedure, (2) the control group of A1 that was challenged with phosphate-buffered saline (PBS), (3) the nasally sensitized group (group A2) that was challenged with OVA by a 25 d procedure, (4)the control group of A2 that was challenged with PBS, (5) the intraperitoneally sensitized group (group B) .The numbers of sneezing after final challenge were counted, and the serum OVA-specific immunoglobulin E (OVA-sIgE), interleukin (IL) -4, IL-13, IL-5 levels in nasal lavage fluid were measured by ELISA. Hematoxylin-eosin staining was performed to evaluate the histological change of nose and lung tissues. Graph Pad Prism 6 software was used to analyze the data.. Nasally sensitized group A1 displayed LAR symptoms of sneezing and eosinophilic infiltrating, but without increased OVA-sIgE in serum on day 10 compared with the control group of A1(t=0.697, P>0.05), OVA-sIgE in serum of group A2(2.710±1.406)ng/ml reached to statistical significance and with airway remodeling on day 25 compared with the control group of A2((0.221±0.080)ng/ml, t=4.329, P<0.05). IL-5 and IL-13 in nasal fluid showed a significant increase in the nasally sensitized group A1, compared with the group A2(t values were 2.442, 2.804, P values were less then 0.05).. A short time intranasal instillation with OVA could establish LAR murine model, continuing OVA challenge could increase serum sIgE level and with airway remodeling. LAR mice show a unique characteristic by expressing higher IL-5 and IL-13 in nose than AR mice, but sIgE in serum remains at a normal level.

Topics: Administration, Intranasal; Animals; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Eosinophils; Immunoglobulin E; Interleukin-13; Interleukin-4; Interleukin-5; Lung; Mice; Mice, Inbred BALB C; Nose; Ovalbumin; Rhinitis, Allergic; Sneezing; Sodium Chloride

This study aimed to explore the effects of curcumin on experimental allergic rhinitis in rats.. Twenty-eight male Wistar albino rats were randomly divided into four groups: a control group; a group in which allergic rhinitis was induced and no treatment given; a group in which allergic rhinitis was induced followed by treatment with azelastine hydrochloride on days 21-28; and a group in which allergic rhinitis was induced followed by treatment with curcumin on days 21-28. Allergy symptoms and histopathological features of the nasal mucosa were examined.. The sneezing and nasal congestion scores were higher in the azelastine and curcumin treatment groups than in the control group. Histopathological examination showed focal goblet cell metaplasia on the epithelial surface in the azelastine group. In the curcumin group, there was a decrease in goblet cell metaplasia in the epithelium, decreased inflammatory cell infiltration and vascular proliferation in the lamina propria.. Curcumin is an effective treatment for experimentally induced allergic rhinitis in rats.

Topics: Administration, Intranasal; Animals; Anti-Allergic Agents; Anti-Inflammatory Agents, Non-Steroidal; Chondrocytes; Cilia; Curcumin; Eosinophils; Goblet Cells; Hyperemia; Hypertrophy; Male; Mast Cells; Metaplasia; Nasal Mucosa; Ovalbumin; Phthalazines; Random Allocation; Rats; Rats, Wistar; Rhinitis, Allergic; Sneezing

Allergic rhinitis (AR) is a common worldwide disease. Animal studies on AR were adopted in various investigations. However, animal studies simply aimed at establishing an animal model for AR have been seldom seen. The purpose of this study was to introduce an easy-to-establish experimental mouse model of AR. To develop a mouse model of AR, 38 Balb/c mice were randomly assigned to two groups. Mice in the study group were sensitized by intraperitoneal (IP) injection of ovalbumin (OVA) on day 1 and 6, followed by continuous inhalation (IH) of OVA solution for 1 week (day 8-14) using a newly designed inhalation box. The control group mice received sensitization of IP normal saline and IH sterilized distilled water instead of OVA. Before and after sensitization, the frequencies of nasal symptoms (sneezing, nasal rubbing) were recorded and the serum levels of total immunoglobulin E (IgE) were evaluated using ELISA. Finally, the murine nasal mucosal tissues were stained by Giemsa solution to estimate the degree of mast cell infiltration. After sensitization by IP and IH OVA, the study group showed significant phenotypic changes including increased sneezing and rubbing. Pathological and cytological findings also confirmed significant elevated serum total IgE titer and local mast cell infiltration in the study group statistically. We successfully developed a workable experimental animal model for AR that was more easily sensitized using our new-designed inhalation box, with less stress and more precisely to be observed.

Topics: Allergens; Animals; Disease Models, Animal; Drug Administration Routes; Immunoglobulin E; Male; Mice; Mice, Inbred BALB C; Nasal Mucosa; Ovalbumin; Rhinitis, Allergic; Sneezing

The objective of the present work was to evaluate anti-allergic effects of intranasal administration of type-A procynidines polyphenols (TAPP) based standardized hydroalcoholic extract of Cinnamomum zeylanicum bark (TAPP-CZ) in ovalbumin (OVA)-induced experimental allergic rhinitis (AR) in BALB/c mice. Sixty male BALB/c mice were divided into six groups of ten each (G1-G6). The mice from G1 were nonsensitized and maintained as normal group. Remaining mice (G2-G6) were sensitized with OVA (500 μL solution, intraperitoneal) on alternate days for 13 days and had twice daily intranasal treatment from day 14-21 as follows: G2 (AR control) received saline, G3 (positive control, XLY) received xylometazoline (0.5 mg/mL, 20 μL/nostril) and G4-G6 received TAPP-CZ (3, 10 and 30 µg/kg in nostril), respectively. On day 21, mice were challenged with OVA (5 μL/nostril, 5% solution) and assessments (nasal signs, biochemical and histopathological) were performed. Treatment with TAPP-CZ (10 and 30 µg/kg in nostril) showed significant attenuation in OVA-induced alterations of the nasal (number of nasal rubbing and sneezing), biochemical markers (serum IgE and histamine), haematological, morphological (relative organ weight of spleen and lung) and histopathological (nasal mucosa and spleen) parameters. In conclusion, TAPP-CZ showed anti-allergic efficacy in animal model of AR.

Topics: Administration, Intranasal; Animals; Anti-Allergic Agents; Biflavonoids; Catechin; Cinnamomum zeylanicum; Disease Models, Animal; Histamine; Immunoglobulin E; Male; Mice; Mice, Inbred BALB C; Ovalbumin; Plant Bark; Plant Extracts; Polyphenols; Proanthocyanidins; Rhinitis, Allergic; Sneezing

Two major distinct subsets of dendritic cells (DCs) are arranged to regulate immune responses: DEC-205+ DCs drive Th1 polarization and 33D1+ DCs establish Th2 dominancy. Th1 polarization can be achieved either by depletion of 33D1+ DCs with a 33D1-specific monoclonal antibody (mAb) or by activation of DEC-205+ DCs via intraperitoneal injection of α-galactosylceramide (α-GalCer). We studied the effect of 33D1+ DC depletion or DEC-205+ DC activation in vivo using an established mouse model of allergic rhinitis (AR).. Mice were injected intraperitoneally with OVA plus alum and challenged 4 times with daily intranasal administration of OVA. Immediately after the last challenge, allergic symptoms such as sneezing and nasal rubbing as well as the number of cells in the bronchoalveolar lavage fluid (BALF) and nasal lavage fluid (NALF) were counted. The levels of serum OVA-specific IgG1, IgG2a, and IgE were also determined by ELISA.. The allergic symptom scores were significantly decreased in 33D1+ DC-depleted or DEC-205+ DC-activated AR mice. The levels of OVA-specific IgG1, IgG2a, and IgE, and the number of NALF cells, but not BALF cells, were reduced in 33D1+ DC-depleted but not in DEC-205+ DC-activated AR mice. Moreover, the activated DEC-205+ DCs suppressed histamine release from IgE-sensitized mast cells, probably through IL-12 secretion.. The manipulation of innate DC subsets may provide a new therapeutic strategy for controlling various allergic diseases by reducing histamine release from IgE-sensitized mast cells by driving the immune response towards Th1 dominancy via activation of DEC-205+ DCs in vivo.

Topics: Alum Compounds; Animals; Bronchoalveolar Lavage Fluid; Cell Count; Cell Lineage; Dendritic Cells; Disease Models, Animal; Female; Galactosylceramides; Histamine Release; Humans; Immunoglobulin E; Immunoglobulin G; Injections, Intraperitoneal; Mast Cells; Mice; Mice, Inbred BALB C; Ovalbumin; Primary Cell Culture; Rhinitis, Allergic; Severity of Illness Index; Sneezing; Th1 Cells; Th2 Cells

Human chemokine-like factor (CKLF1) is a human cytokine that exhibits chemotactic activities on a wide spectrum of leukocytes. One of CKLF1's C-terminal peptides, C19, exerts inhibitory effects on chemotaxis mediated by mouse Ccr3 and Ccr4 and human CCR3 and CCR4. Mouse models of asthma show that C19 can also inhibit the Th2 response. CCR3 and CCR4 are chemokine receptors important to allergic rhinitis, a condition whose pathogenesis is similar to that of asthma. Here, we established a mouse model of allergic rhinitis by repetitive sensitization and intranasal challenge with OVA and assessed whether C19 has therapeutic effects on this model. In this study, both intranasal and intraperitoneal administration of C19 reduced allergic symptoms such as sneezing and rubbing and serum concentration of IgE. C19 showed a strong ability to suppress eosinophil accumulation in nasal mucosa and lung tissues. C19 was able to suppress the Th2 cytokine IL-4 without augmenting the Th1 cytokine IFN-γ in BAL and IL-4(+) cells in the local nasal tissue. In terms of symptom amelioration, IgE reduction, and eosinophilia suppression, C19 was found to be as effective against allergic rhinitis as Budesonide. Moreover, intranasal treatment has a stronger therapeutic effect than other types of administration, and it may be more convenient and safe. For these reasons, C19 may have potential in the treatment of allergic rhinitis.

Topics: Administration, Intranasal; Animals; Anti-Inflammatory Agents; Bronchoalveolar Lavage Fluid; Budesonide; Disease Models, Animal; Eosinophils; Female; Immunoglobulin E; Interferon-gamma; Interleukin-4; Lung; MARVEL Domain-Containing Proteins; Membrane Proteins; Mice; Mice, Inbred BALB C; Nasal Mucosa; Ovalbumin; Peptides; Repressor Proteins; Rhinitis, Allergic, Perennial; Sneezing

Previous studies have shown that peroxisome proliferator-activated receptor gamma (PPARgamma) is involved in allergic rhinitis. It has been reported that 5-aminosalicylate (5-ASA) has an affinity for PPARgamma, but the effects of 5-ASA on the nasal symptoms of allergic rhinitis are unclear. This study aimed to clarify the effects of 5-ASA on nasal symptoms in an allergic rhinitis model in mice. Female BALB/c mice were sensitized by intraperitoneal injection of ovalbumin (OVA) and aluminium hydroxide hydrate gel (alum) on days 0, 5, 14 and 21. Seven days later, mice were sensitized by the intranasal application of OVA thrice a week. 5-ASA was also administered orally after instillation of the antigen from day 28. The severity of allergic rhinitis was assessed by determining the extent of 2 nasal allergic symptoms-sneezing and nasal rubbing. In addition, serum OVA-specific immunoglobulin E (IgE) antibody, interleukin (IL)-4, and IL-10 levels in nasal lavage fluid and histamine sensitivity were determined. Repeated oral administration of 5-ASA attenuated the progression of nasal symptoms in sensitized mice in a dose-dependent manner. Additionally, 5-ASA prevented an increase in histamine sensitivity. Finally, 5-ASA inhibited both OVA-specific IgE antibody and IL-4 production; however, it had no effect on IL-10 levels. These results indicate that 5-ASA has a prophylactic effect on allergic rhinitis.

Topics: Aluminum Hydroxide; Animals; Anti-Allergic Agents; Female; Histamine; Immunoglobulin E; Interleukin-10; Interleukin-4; Mesalamine; Mice; Mice, Inbred BALB C; Nasal Lavage Fluid; Ovalbumin; PPAR gamma; Rhinitis, Allergic, Perennial; Sneezing

Peroxisome proliferator-activated receptor gamma(PPAR-gamma) has been shown to play an important role in the control of inflammatory responses acting on macrophages, mast cells, T cells, and eosinophils. The present study was aimed at investigating the effects of PPAR-gamma agonist on nasal symptoms and eosinophil accumulations in nasal mucosa by using a murine allergic rhinitis model. Furthermore, we examined the expression of PPAR-gamma in the nasal mucosa in mice.. BALB/c mice were sensitized and challenged intranasally with ovalbumin. Ciglitazone, a PPAR-gamma agonist, was administered orally 6 hours before each nasal challenge.. Administration of PPAR-gamma agonist significantly decreased the number of nasal rubs, nasal histamine responsiveness, serum IgE, IL-5 production from the spleen, and eosinophilic infiltration in the nasal mucosa. Furthermore, PPAR-gamma was expressed in eosinophils and epithelial cells in the nasal mucosa by immunohistochemistry.. PPAR-gamma was expressed in eosinophils and epithelial cells in the nasal mucosa. Also, the oral administration of ciglitazone is effective in upper airway allergic inflammation in mice.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Behavior, Animal; Eosinophils; Epithelial Cells; Female; Histamine; Immunoglobulin E; Interferon-gamma; Interleukin-13; Interleukin-5; Mice; Mice, Inbred BALB C; Nasal Mucosa; Ovalbumin; PPAR gamma; Rhinitis, Allergic, Perennial; Sneezing; Spleen; Thiazolidinediones

Unrestrained plethysmography has been used to monitor bronchoconstriction because of its ease of use and ability to measure airway responsiveness in conscious animals. However, its reliability remains controversial.. To investigate if unrestrained plethysmography could provide a valid interpretation of airway responsiveness in allergic BALB/c mice.. Ovalbumin sensitized BALB/c mice were randomized to receive either a single-dose Ovalbumin challenge (OVA-1D group) or a three-dose Ovalbumin challenge (OVA-3D group). The OVA-1D group was further divided into OVA-1D-I (measured invasively, using lung resistance as the index of responsiveness) and OVA-1D-N group (measured non-invasively, using Penh as the index of responsiveness). Similarly the OVA-3D group was divided into OVA-3D-I and OVA-3D-N groups based on the above methods. The control groups were sensitized and challenged with normal saline. Bronchial alveolar lavage fluid was taken and airway histopathology was evaluated for airway inflammation. Nasal responsiveness was tested with histamine challenge.. Compared with controls, a significant increase in airway responsiveness was shown in the OVA-1D-N group (P < 0.05) but not in the OVA-1D-I group. Both OVA-3D-I and OVA-3D-N groups showed higher responsiveness than their controls (P < 0.05). The nasal mucosa was infiltrated by eosinophic cells in all Ovalbumin immunized groups. Sneezing or nasal rubbing in allergic groups appeared more frequent than that in the control groups.. Penh can not be used as a surrogate for airway resistance. The invasive measurement is specific to lower airway. Penh measurement (done as a screening procedure), must be confirmed by a direct invasive measurement specific to lower airway in evaluating lower airway responsiveness.

Topics: Administration, Intranasal; Airway Resistance; Animals; Bronchoalveolar Lavage Fluid; Eosinophils; Female; Histamine; Inflammation; Injections, Intraperitoneal; Mice; Mice, Inbred BALB C; Nasal Mucosa; Ovalbumin; Plethysmography; Respiratory Hypersensitivity; Respiratory System; Sneezing

Glucocorticoids play an important role in modulating allergic inflammation and immune response. However, little is known about the role of endogenous glucocorticoids in airway allergic disease.. To investigate the effects of endogenous glucocorticoids on regulating allergic inflammation and T(H)1/T(H)2 balance in an airway allergic murine model.. An ovalbumin-sensitized murine model was established by intraperitoneal injection sensitization and intranasal challenge with ovalbumin. Glucocorticoid release was inhibited by administration of metyrapone, and the peripheral glucocorticoid receptors were blocked by administration of RU486. The numbers of eosinophils in the lung, peripheral blood, and bone marrow were quantified. The changes in T(H)2/T(H)1 cells were investigated by flow cytometry, and their cytokines were tested by enzyme-linked immunosorbent assay, including interleukin 4, interleukin 5, and interferon gamma, in the supernatant of the spleen cell culture.. Inhibition of endogenous glucocorticoids caused more sneezing and further increased eosinophil counts in the peripheral blood and bone marrow of the sensitized mice. However, by inhibition of endogenous glucocorticoids, the interferon gamma levels were upregulated, the interleukin 4 and 5 levels were down-regulated, and the ratio of T(H)2/T(H)1 cells decreased significantly, indicating a shift to a T(H)1-predominant immune response in sensitized mice.. Our findings suggest that endogenous glucocorticoids play an important role in abating allergic inflammatory reaction and modulating the T(H)1/T(H)2 balance in an airway allergic murine model. Inhibition of endogenous glucocorticoids resulted in a shift to T(H)1 predominance, but that did not attenuate the severity of the allergic inflammatory reaction.

Topics: Animals; Bone Marrow; Cell Count; Concanavalin A; Corticosterone; Eosinophils; Glucocorticoids; Immunization; Inflammation; Interferon-gamma; Interleukin-4; Interleukin-5; Leukocyte Count; Lung; Lymphocyte Activation; Lymphocytes; Male; Metyrapone; Mice; Mice, Inbred BALB C; Mifepristone; Ovalbumin; Respiratory Hypersensitivity; Sneezing; Specific Pathogen-Free Organisms; Spleen; Th1 Cells; Th2 Cells

KP-496 is a novel dual antagonist for leukotriene (LT) D(4) and thromboxane (TX) A(2) receptors. We investigated effects of KP-496 on antigeninduced nasal blockage in 2 guinea pig models of allergic rhinitis.. Male Hartley guinea pigs were used.. Animals were actively sensitized with ovalbumin (OVA) or Japanese cedar pollen, and were then repeatedly challenged with OVA or pollen, respectively. KP-496 (0.003 %-0.05 %) was intranasally administered 0.5 or 1 h before and 2 h after an antigen challenge.. As an indicator of nasal blockage, specific airway resistance was measured using a double-flow plethysmograph system. Statistical analyses were performed with Dunnett's test (OVA model) or t-test (pollen model).. Although early phase response was not affected by even a high dose (0.03 %) of KP-496, late phase nasal blockage (1.68 +/- 0.26) was inhibited by 0.01 % (0.87 +/- 0.19; p <0.05) and 0.03 % (0.44 +/- 0.12; p <0.01) of KP-496 in the OVA model. On the other hand, both early (5.60 +/- 0.77) and late phase responses (7.90 +/- 1.70) were inhibited by 0.05 % KP-496 to 2.68 +/- 0.84 (p <0.05) and 2.71 +/- 0.83 (p <0.05), respectively, in the pollen model, in which nasal hyperresponsiveness had been acquired by multiple challenges.. KP-496 may be clinically effective for nasal blockage in allergic rhinitis.

Topics: Airway Resistance; Animals; Area Under Curve; Benzoates; Disease Models, Animal; Guinea Pigs; Humans; Leukotriene Antagonists; Male; Nasal Mucosa; Nasal Obstruction; Ovalbumin; Pollen; Receptors, Leukotriene; Receptors, Thromboxane A2, Prostaglandin H2; Rhinitis, Allergic, Perennial; Sneezing; Thiazoles

Ovalbumin-induced guinea pig model of rhinitis was assessed for its utility in the studies of rhinitis. Systemic sensitization and challenge with ovalbumin-induced rhinitis symptoms and an increase in anti-OVA-IgE and IgG titers, positive skin reactions and nasal lavage IL-4 concentration. Histopathology of nasal mucosa showed infiltration of eosinophils and other inflammatory cells consistent with the symptoms. Topical sensitization of ovalbumin yielded inconsistent symptoms of rhinitis. In systemic sensitization model, repeated challenge of ovalbumin caused similar response for at least 3 consecutive challenges. The symptoms were affected by relative humidity in the air and dosing volume of topical drugs. Sneezing and lacrimation were reduced by acute oral administration of the H1 receptor antagonists and steroids or the prophylactic oral administration of cysteinyl leukotriene (CysLT1) receptor antagonist montelukast or acute topical antihistamines, mast cell stabilizer sodium cromoglycate and anticholinergic agent ipratropium bromide, but not by a topical steroid. Nose rubbing was reduced significantly by some oral and topical antihistamines. Oral steroids offered excellent protection against all symptoms. Dexamethasone and montelukast also inhibited nasal lavage IL-4 concentration and inflammatory cell infiltration. Treatment with topical steroid fluticasone for 2 weeks had no effect on sneezing or rubbing. However, it caused complete inhibition of congestion. The cyclooxygenase inhibitor indomethacin had no effect on symptoms of rhinitis. The adrenergic alpha receptor agonist-decongestant oxymetazoline caused reduction in congestion. These results suggest that differential responsiveness to symptoms of rhinitis by a new agent can be very well profiled in the model in congruence with the mediation pathways and mechanism of action of drugs. The model provides complete symptomatic characterization of rhinitis and is a good tool for its study.

Topics: Administration, Oral; Administration, Topical; Animals; Anti-Allergic Agents; Disease Models, Animal; Female; Guinea Pigs; Humidity; Immunoglobulin E; Immunoglobulin G; Interleukin-4; Male; Ovalbumin; Passive Cutaneous Anaphylaxis; Rhinitis, Allergic, Perennial; Sneezing

The present study was performed to study the participation of histamine H(3) receptors in nasal symptoms using Sch 50971, a potent and selective agonist of the H(3) receptor. Repeated topical application of antigen caused an increase in sneezing and nasal rubbing in sensitized mice. Oral administration of Sch 50971 and imetit, specific H(3)-receptor agonists, resulted in an inhibition of nasal symptoms induced by an antigen similar to an H(1)-receptor antagonist, cetirizine. Furthermore, simultaneous use of H(3)-receptor agonists, Sch 50971 or imetit, and an H(1)-receptor antagonist, cetirizine, caused a significant inhibitory effect on nasal symptoms at doses that showed no effect when used separately. The number of eosinophils in the nasal mucosa of mice sensitized with antigen was significantly decreased by cetirizine; however, Sch 50971 and imetit had no effect on eosinophil infiltration. These results clearly indicate that H(3) receptors are involved in the etiology of nasal allergy, and the stimulation of H(3) receptors may be useful as a novel therapeutic approach in nasal allergy.

Topics: Animals; Anti-Allergic Agents; Cetirizine; Chemotaxis, Leukocyte; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Synergism; Eosinophils; Female; Histamine Agonists; Histamine H1 Antagonists, Non-Sedating; Imidazoles; Mice; Mice, Inbred BALB C; Nasal Mucosa; Ovalbumin; Pruritus; Pyrrolidines; Receptors, Histamine H3; Rhinitis, Allergic, Perennial; Sneezing; Thiourea; Time Factors

Different drugs from various pharmacological classes were compared for their ability to protect against the nasal effects of acute allergen challenge in a guinea pig model. In the model, sneezing and nose rubbing were recorded after an initial allergen challenge in guinea pigs previously sensitized to egg albumin. Four days later the same guinea pigs were re-challenged a second time when anesthetised. In these anaesthetized animals, nasal airway pressure, pulmonary inflation pressure and cellular infiltration into nasal lavage fluid were measured. The drug tested were autacoid antagonists (mepyramine--3mg/kg, cetirizine--3mg/kg and montelukast--10mg/kg), L-NAME (10 or 20mg/kg), heparin (20mg/kg) and dexamethasone (20mg/kg) given either intraperitoneally or intravenously; all were given shortly before challenge. Sneezing induced by allergen challenge was statistically significantly reduced by mepyramine, cetirizine and dexamethasone whereas only cetirizine reduced nose rubbing. Changes in nasal airway pressure due to allergen exposure were reduced by cetirizine, montelukast, L-NAME, and heparin, but not by mepyramine, nor dexamethasone. In the presence of L-NAME, nasal airway pressure actually changed in the opposite direction. Cellular infiltration, as assessed by cytometry in nasal lavage fluid 60min after acute allergen challenge, was reduced by montelukast and heparin but not by antihistamines, L-NAME nor dexamethasone. This pattern of effects of the drugs, given by doses and routes previously described in the literature as being effective was not completely consistent with expected responses. The lack of effect of dexamethasone probably reflects the fact that it was given acutely whereas in the clinic chronic administration is used. The two antihistamines were not identical in their actions, presumably reflecting the fact that cetirizine has therapeutic actions not entirely confined to blockade of H1 receptors. Montelukast has not been reported to have major effects on sneezing and itching in the clinic but reduces nasal obstruction (lower nasal airway pressure or nasal patency). Montelukast's effects on cellular infiltration indicate the possible involvement of leukotrienes. Heparin has actions on inflammatory cell infiltration. This could explain its profile of reducing both cellular infiltration, and increased nasal airway pressure.

Topics: Acetates; Acute Disease; Animals; Cetirizine; Cyclopropanes; Dexamethasone; Disease Models, Animal; Guinea Pigs; Heparin; Histamine H1 Antagonists; Male; Nasal Obstruction; NG-Nitroarginine Methyl Ester; Ovalbumin; Pyrilamine; Quinolines; Rhinitis, Allergic, Seasonal; Sneezing; Sulfides

The present study was undertaken to investigate the involvement of chemical mediators in nasal allergic responses using histidine decarboxylase knockout (HDC-KO) mice. An allergic rhinitis model was developed in HDC-KO and wild-type mice by the intraperitoneal injection of ovalbumin, aluminum hydroxide gel and pertussis toxin. Five days later, they were boosted by a subcutaneous injection of ovalbumin into the back. From day 18 after the first immunization to day 39, intranasal sensitization with ovalbumin was performed every day and the severity of allergic rhinitis was observed by measuring nasal allergic responses and total IgE levels. It was found that the intranasal administration of antigen caused a significant increase of nasal sneezing and rubbing from day 25 to day 39 both in sensitized HDC-KO and wild-type mice. In addition, a significant elevation of total IgE levels in serum was also found both in sensitized HDC-KO and wild-type mice from day 18 to day 39 after the first immunization. L-733,060, a tachykinin NK(1) receptor antagonist at a dose of 10 mg/kg (s.c.), resulted in the dose-dependent inhibition of nasal allergic responses induced by antigen in both HDC-KO and wild-type mice. In addition, both chlorpheniramine at doses of 3 and 10 mg/kg (p.o.) and BW A868C at doses of 0.3 and 1 mg/kg (i.v.) also showed a dose-related reduction of the nasal allergic responses induced by antigen in sensitized wild-type mice. On the other hand, they had no effects on the nasal signs induced by antigen in HDC-KO mice. From these results, it was revealed that substance P induces nasal allergic responses in the mouse model of chronic allergic rhinitis through the activation of tachykinin NK(1) receptors. Therefore, it can be concluded that not only histamine, but also substance P and prostaglandin D(2), participated in the nasal allergic responses induced by antigen in mice.

Topics: Animals; Behavior, Animal; Chlorpheniramine; Histamine H1 Antagonists; Histidine Decarboxylase; Hydantoins; Immunization; Immunoglobulin E; Inflammation Mediators; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Neurokinin-1 Receptor Antagonists; Ovalbumin; Piperidines; Receptors, Immunologic; Receptors, Prostaglandin; Rhinitis, Allergic, Seasonal; Sneezing; Substance P

Konjac is a traditional Japanese food with a peculiar texture, and it has been suggested that its main ingredient, konjac glucomannan (KGM), ameliorates metabolic disorders such as diabetes and hypercholesteremia. We have found that feeding with pulverized KGM (PKGM) prevents skin inflammation in a murine model of atopic dermatitis. Here, we show that dietary PKGM suppresses allergic rhinitis-like symptoms in mice upon immunization and nasal sensitization with ovalbumin (OVA). The PKGM-fed mice showed a much lower frequency of sneezing than in control animals. We also found that PKGM supplementation exclusively suppressed OVA-specific IgE response without affecting IgG1/IgG2a responses as well as systemic Th1/Th2 cytokine production. These results suggest that PKGM can be a beneficial foodstuff in preventing nasal allergy such as seasonal pollinosis.

Topics: Administration, Oral; Animals; Cells, Cultured; Dietary Carbohydrates; Enzyme-Linked Immunosorbent Assay; Female; Immunoglobulin E; Interferon-gamma; Interleukin-4; Interleukin-5; Mannans; Mice; Mice, Inbred BALB C; Molecular Weight; Monocytes; Ovalbumin; Powders; Rhinitis, Allergic, Seasonal; Sneezing; Spleen; Viscosity

We investigated the effect of Lactobacillus acidophilus strain L-55 isolated from infant feces on experimental allergic rhinitis in BALB/c mice. The heat-treated cells of strain L-55 were orally administrated for 4 consecutive weeks to mice sensitized by ovalbumin (OVA), and nasal symptoms (sneezing and nasal rubbing) induced by OVA challenge were evaluated. Strain L-55 at doses of 1 and 10 mg cells/mouse significantly inhibited nasal symptoms by repeated administration over a period of 2 weeks. Furthermore, we measured the level of OVA-specific IgE titers in the serum by passive cutaneous anaphylaxis (PCA) reaction. PCA titers in the sera from mice administrated strain L-55 were significantly lowered compared with the control. These results suggest that oral administration of strain L-55 may be useful for alleviating the nasal symptoms of allergic rhinitis.

Topics: Administration, Oral; Animals; Behavior, Animal; Disease Models, Animal; Feces; Female; Humans; Immunoglobulin E; Infant; Lactobacillus acidophilus; Mice; Mice, Inbred BALB C; Ovalbumin; Passive Cutaneous Anaphylaxis; Rhinitis, Allergic, Perennial; Sneezing

Cough is a common and important symptom of asthma and allergic rhinitis. Previous experimental evidence has shown enhanced cough sensitivity during early phase of experimental allergic rhinitis in guinea pigs. We hypothesized that airway inflammation during the late phase response after repeated nasal antigen challenge may affect the afferent sensory nerve endings in the larynx and tracheobronchial tree and may also modulate cough response. In the present study we evaluated the cough sensitivity during a period of early and late allergic response in sensitized guinea pigs after repeated nasal antigen challenges. Forty-five guinea pigs were sensitized with ovalbumin (OVA). Four weeks later 0.015 ml of 0.5 % OVA was intranasally instilled to develop a model of allergic rhinitis that was evaluated from the occurrence of typical clinical symptoms. Animals were repeatedly intranasally challenged either by OVA (experimental group) or by saline (controls) in 7-day intervals for nine weeks. Cough was elicited by inhalation of citric acid aerosols. Cough was evaluated at 1 or 3 h after the 6th nasal challenge and 17 or 24 h after the 9th nasal challenge. The cough reflex was significantly increased at 1 and 3 h after repeated nasal challenge in contrast to cough responses evoked at 17 and 24 h after repeated nasal challenge. In conclusion, enhanced cough sensitivity only corresponds to an early allergic response after repeated nasal challenges.

Topics: Allergens; Animals; Citric Acid; Cough; Disease Models, Animal; Guinea Pigs; Immunization; Male; Nasal Provocation Tests; Ovalbumin; Respiratory System; Rhinitis, Allergic, Perennial; Sneezing; Time Factors

Jia Wei Cang Er Zi San, a traditional Chinese herbal formula, has been used to treat allergic rhinitis (AR) for several centuries. However, its effect on experimental animal models and its therapeutic mechanism remain unclear.. To study the effect of Shu-Bi-Lin, a modified Jia Wei Cang Er Zi San, on an animal model of AR.. Shu-Bi-Lin was administered to the guinea pig model of AR. Meanwhile, an antihistamine-treated group for the treatment control, an ovalbumin-sensitized and untreated group for the positive control, and a sham-sensitized, sham-challenged group for the sham control were studied in parallel. Symptomatic and some pathophysiologic variables were evaluated.. Sneezing and nasal scratching after challenges were significantly ameliorated in the Shu-Bi-Lin-treated group compared with the ovalbumin-sensitized and untreated group, but rhinorrhea volume was not reduced. Shu-Bi-Lin significantly suppressed the production of IgG1 in the passive cutaneous anaphylaxis test. The thromboxane B2 level in nasal lavage fluid was significantly deceased in the Shu-Bi-Lin-treated group; however, the reduction in histamine and peptide leukotriene levels did not reach statistical significance. In addition, eosinophil infiltration and endothelial nitric oxide synthase immunoreactivity in the nasal tissues were reduced in the Shu-Bi-Lin-treated group.. Shu-Bi-Lin could alleviate the nasal symptoms of AR, and its mechanism might be related to its inhibitory effect on type I anaphylaxis reactions and eosinophil infiltration in the nasal tissues, as well as the inhibition of some mediators related to AR.

Topics: Animals; Anti-Allergic Agents; Disease Models, Animal; Drugs, Chinese Herbal; Eosinophils; Guinea Pigs; Histamine; Histamine H1 Antagonists, Non-Sedating; Immunoglobulin E; Immunoglobulin G; Leukotrienes; Loratadine; Nasal Lavage Fluid; Nasal Mucosa; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; Ovalbumin; Rhinitis; Sneezing; Thromboxane B2

This study was undertaken to investigate the involvement of cyclooxygenase-2 (COX-2) in allergic nasal inflammation in actively sensitized rats. An allergic rhinitis model was developed by the repeated topical application of antigen into the nasal cavities in the sensitized rats. The severity of allergic rhinitis was studied by measuring the nasal behavior, as well as electroencephalogram (EEG) activity by antigen challenge. The electrodes were implanted chronically into the bilateral olfactory bulb of the rats and the EEG was measured monopolarly with an electroencephalograph (EEG, Nohon Kohden, Japan). The intranasal application of antigen caused the increase of nasal allergic signs as well as an EEG spike in a dose-dependent fashion, and at a dose of 50 microg/site, it showed a significant effect. The responses induced by the antigen were evaluated with certain drugs, etodolac (a selective COX-2 inhibitor), indomethacin (a non-selective COX inhibitor), ramatroban (a thromboxane A2 receptor antagonist) and zafirlukast (a cys-leukotriene receptor antagonist). Etodolac showed the inhibition of nasal behavior and EEG spike in a dose-related fashion, and at doses of 3 and 10 mg/kg, it showed a significant effect. Moreover, ramatroban also caused the dose-related inhibition of nasal behavior and EEG spike induced by antigen. On the other hand, both indomethacin and zafirlukast had no effects on the responses induced by antigen, even at a higher dose. Therefore, it can be concluded that cyclooxygenase-2 actively participates in the allergic nasal inflammation in actively sensitized rats.

Topics: Animals; Carbazoles; Cyclooxygenase 2; Cyclooxygenase Inhibitors; Disease Models, Animal; Electroencephalography; Etodolac; Hypersensitivity; Indoles; Indomethacin; Leukotriene Antagonists; Male; Olfactory Bulb; Ovalbumin; Phenylcarbamates; Rats; Rats, Wistar; Receptors, Thromboxane A2, Prostaglandin H2; Rhinitis; Sneezing; Sulfonamides; Tosyl Compounds

Our previous study revealed that exposure to 0.4 ppm ozone (O(3)) enhanced nasal allergy-like reactions in guinea pigs. In the present study, we investigated the concentration-dependency of the effects of exposure to O(3) on the aggravation of nasal allergy-like reactions induced by repeated nasal administration of antigen. Guinea pigs were exposed to filtered air or 0.1-0.6 ppm O(3) for 5 weeks. After each weekly administration of ovalbumin (OVA), sneezes and nasal secretions were measured. The number of eosinophils infiltrating the nasal septum and the titers of OVA-specific antibody were measured 24h after the last administration. Ozone increased sneezing and nasal secretion induced by OVA, nasal responsiveness to physical stimuli, and the number of infiltrating eosinophils in a concentration-dependent manner. The titer of anti-OVA-IgG was increased in animals exposed to 0.6 ppm O(3). Thus, exposure to O(3) aggravated nasal allergy-like symptoms concentration dependently. The aggravation was caused by induction of nasal hyperresponsiveness, the infiltration of eosinophils, and the increase in the production of anti-OVA-IgG. The estimated maximum likelihood estimation concentrations (MLECs) and bench mark concentrations (BMCs) of O(3) for these indices were in the range of 0.09-0.18 and 0.02-0.06 ppm, respectively.

Topics: Administration, Inhalation; Animals; Benchmarking; Dose-Response Relationship, Drug; Eosinophils; Guinea Pigs; Immunoglobulin G; Male; Nasal Mucosa; Ovalbumin; Oxidants, Photochemical; Ozone; Rhinitis, Allergic, Perennial; Sneezing

TAK-427 (2-[6-[[3-[4-(diphenylmethoxy)piperidino]propyl]amino]imidazo[1,2-b]pyridazin-2-yl]-2-methylpropionic acid dihydrate) is a novel anti-allergic agent that has both histamine H1-receptor antagonist and anti-inflammatory activities. In this study, we evaluated the efficacy of TAK-427 on acute nasal responses and nasal obstruction using various guinea pig models of allergic rhinitis. TAK-427 inhibited the histamine-induced nasal reactions with an ID50 value of 0.633 mg/kg, p.o. TAK-427 (0.1-10 mg/kg, p.o.) and most histamine H1-receptor antagonists tested inhibited the increase in intranasal pressure, nasal hypersecretion, sneezing and nasal itching caused by a single antigen challenge in sensitized guinea pigs. In addition, TAK-427 (0.3, 30 mg/kg, p.o.) significantly inhibited the development of nasal obstruction when sensitized guinea pigs were repeatedly challenged via inhalation with Japanese cedar pollen, whereas the histamine H1-receptor antagonist, azelastine (1 mg/kg, p.o.), and ketotifen (1 mg/kg, p.o.) were without effect. These results suggest that TAK-427 might not only suppress acute nasal symptoms but also ameliorate nasal obstruction via the effects other than those as a histamine H1-receptor antagonist.

Topics: Acute Disease; Animals; Anti-Inflammatory Agents; Disease Models, Animal; Guinea Pigs; Histamine; Histamine H1 Antagonists; Imidazoles; Male; Nasal Obstruction; Ovalbumin; Pollen; Pyridazines; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Sneezing

The purpose of this study was to investigate the involvement of chemical mediators other than histamine in nasal allergic signs using histamine H(1) receptor-deficient mice. In passively sensitized mice, antigen instillation into the nasal cavity induced significant increases in sneezing and nasal rubbing in wild-type mice, but no such increases were observed in histamine H(1) receptor-deficient mice. In actively sensitized mice, both sneezing and nasal rubbing were also significantly increased in a dose-dependent manner in both wild-type and histamine H(1) receptor-deficient mice. Histamine H(1) receptor antagonists such as cetirizine and epinastine significantly inhibited antigen-induced nasal allergic signs in wild-type mice, although the effects were incomplete. In addition, the thromboxane A(2) receptor antagonist ramatroban also inhibited these responses in wild-type mice. However, the leukotriene receptor antagonist zafirlukast showed no effects in wild-type mice. These results suggested that in the acute allergic model (passive sensitization), only histamine H(1) receptors are related to nasal signs induced by antigen, whereas in the chronic allergic model (active sensitization), both histamine H(1) receptors and thromboxane A(2) receptors were involved in the responses.

Topics: Animals; Anti-Allergic Agents; Antigens; Behavior, Animal; Carbazoles; Cetirizine; Dose-Response Relationship, Drug; Female; Histamine H1 Antagonists; Immunization; Immunoglobulin E; Indicators and Reagents; Indoles; Leukotriene Antagonists; Mice; Mice, Knockout; Ovalbumin; Passive Cutaneous Anaphylaxis; Phenylcarbamates; Receptors, Histamine H1; Rhinitis, Allergic, Seasonal; Sneezing; Sulfonamides; Thromboxane A2; Tosyl Compounds

The ability of O3 exposure to aggravate ovalbumin (OVA)-induced nasal allergy-like symptoms was studied in guinea pigs. Guinea pigs were exposed to filtered air or to 0.4 ppm O3 for 5 weeks. During the exposure, 1% OVA or saline was administered into the nasal cavities once a week. Sneezes and nasal secretions were measured for a 20-min period following OVA administration. The number of eosinophils infiltrating both nasal epithelium and subepithelium and titers of specific anti-OVA-IgG were measured 24 h after the last administration. Ozone increased OVA-induced sneezing and nasal secretion, as well as induced nasal hyper-responsiveness to physical stimuli. The number of eosinophils infiltrating the nasal subepithelium was increased by O3, and the titer of anti-OVA-IgG tended to increase in the O3-exposed animals. Thus, exposure to O3 aggravated nasal allergy-like symptoms by inducing nasal hyper-responsiveness, the infiltration of eosinophils, and by tending to increase the production of anti-OVA-IgG.

Topics: Administration, Intranasal; Animals; Antibody Specificity; Eosinophils; Guinea Pigs; Immunoglobulin E; Immunoglobulin G; Male; Nasal Mucosa; Ovalbumin; Ozone; Rhinitis, Allergic, Perennial; Sneezing

An animal model of chronic allergic rhinitis was developed by repeated local booster sensitization into the nasal cavity in sensitized rats. The severity of allergic rhinitis was assessed by determining the extent of two markers of nasal allergic symptoms (sneezing and nasal rubbing) after antigen challenge. The number of incidents of sneezing and nasal rubbing was markedly increased during intranasal instillation of antigen in sensitized rats. The PCA titers were also markedly elevated by intranasal sensitization. Some histamine H(1)-receptor antagonists such as chlorpheniramine, ketotifen, astemizole and epinastine inhibited the increase in antigen-induced nasal symptoms in a dose-related manner. Nasal rubbing was more potently inhibited by H(1)-receptor antagonists than sneezing. In conclusion, we developed a chronic allergic rhinitis model showing nasal symptoms in rats, and this model may be useful for evaluating the effects of drugs on allergic rhinitis.

Topics: Allergens; Animals; Anti-Allergic Agents; Astemizole; Chlorpheniramine; Dibenzazepines; Disease Models, Animal; Dose-Response Relationship, Drug; Histamine H1 Antagonists; Imidazoles; Immunization; Ketotifen; Nasal Cavity; Ovalbumin; Passive Cutaneous Anaphylaxis; Rats; Rats, Wistar; Rhinitis, Allergic, Perennial; Sneezing; Time Factors

Diesel exhaust particulates (DEP) () and exposure to diesel exhaust (DE) induce nasal mucosal hyperresponsiveness to histamine. Therefore, in the present study, we investigated whether or not exposing guinea pigs to DE aggravates the nasal allergic reaction induced by repeated nasal administration of ovalbumin (OVA). Guinea pigs were exposed to filtered air or to DE (DE containing 0.3 or 1.0 mg/m(3) of DEP) for 5 wk. During exposure to filtered air or to DE, guinea pigs were administered 1% of OVA in saline into the nasal cavities once a week. Sneezes were counted and nasal secretions were measured as indices of sneezing responses and rhinorrhea for 20 min after OVA administration. Titers of specific anti-OVA-IgG and anti-OVA-IgE and the number of eosinophils infiltrated into both nasal epithelium and subepithelium were measured at the end of the exposure to DE. Exposure to DE enhanced the number of sneezes and the amount of nasal secretions induced by OVA. Titers of specific anti-OVA-IgG and anti-OVA-IgE also significantly increased in DE-exposed animals. Exposure to DE also augmented the number of eosinophils that infiltrated both the nasal epithelium and the subepithelium induced by OVA. These results suggest that exposure to DE enhances the nasal allergic reaction induced by repeated antigen administration in guinea pigs.

Topics: Animals; Eosinophils; Guinea Pigs; Immunoglobulin E; Immunoglobulin G; Leukocyte Count; Nasal Mucosa; Ovalbumin; Respiratory Hypersensitivity; Sneezing; Vehicle Emissions

Ag-specific T cell activation requires the engagement of T cell receptor (TCR) with antigen in the context of MHC, and the engagement of appropriate costimulatory molecules. It is well established that B7/CD28-CTLA4 costimulatory pathway plays an important role in the induction of T helper (Th) cells in T-cell dependent immune reactions. In this study, we evaluated the effects of blocking the costimulatory pathway by systemic administration of CTLA4-Ig during repeated nasal antigen challenges in systemically presensitized mouse. The antigen-induced early phase nasal symptoms, nasal hyperresponsiveness to histamine and nasal eosinophilia were significantly suppressed by CTLA4-Ig treatment. Elevation of serum level of antigen-specific IgE, but not IgG1 or IgG2a was inhibited by the treatment. In relation to cytokine levels in the tissue extracts of the nasal mucosa, an up-regulation of IL-4 was significantly inhibited, however, the levels of IL-5 and IFN-gamma were not affected by the treatment. These results suggest that B7/CD28-CTLA4 costimulatory pathway plays an important role in on-going Th2-related allergic reactions in the nose.

Topics: Abatacept; Animals; Antigens, CD; Antigens, Differentiation; CTLA-4 Antigen; Cytokines; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Eosinophils; Histamine; Immunoconjugates; Immunoglobulins; Immunosuppressive Agents; Male; Mice; Mice, Inbred BALB C; Nasal Lavage Fluid; Nasal Mucosa; Ovalbumin; Recombinant Fusion Proteins; Rhinitis, Allergic, Perennial; Sneezing; Specific Pathogen-Free Organisms

The effects of two tachykinin receptor antagonists, FK888 (selective antagonist at the tachykinin NK-1 receptor) and FK224 (dual antagonist at NK-1 and NK-2 tachykinin receptors), on the frequency of sneezing, decrease of nasal patency, and increase of vascular dye leakage induced by antigen challenge upon the guinea-pig nasal mucosa were studied. The animals were sensitized with ovalbumin intraperitoneally. FK224 inhibited and FK888 tended to inhibit the decrease of nasal patency induced by antigen challenge. The increase of vascular dye leakage from nasal mucosa induced by antigen challenge tended to be inhibited by both FK224 and FK888. But both of them did not inhibit the increase of sneezing induced by antigen challenge. We conclude that in the guinea-pig model of nasal allergy, tachykinin receptors mediate plasma leakage and swelling of nasal mucosa induced by antigen challenge, but the participation of an axonal reflex via tachykinin receptors is rather small compared to the direct vascular effect of chemical mediators.

Topics: Airway Resistance; Animals; Antigens; Capillary Permeability; Dipeptides; Female; Guinea Pigs; Indoles; Neurokinin-1 Receptor Antagonists; Ovalbumin; Peptides, Cyclic; Receptors, Neurokinin-1; Receptors, Neurokinin-2; Respiratory Hypersensitivity; Sneezing; Statistics, Nonparametric

To define the role of platelet activating factor (PAF) in allergic rhinitis, we examined the effects of anti-PAF agents (WEB2086, SM10661) on the changes of nasal airway resistance (NAR) and nasal symptoms after topical antigen challenge in actively sensitized guinea pigs and compared these with the changes brought by anti-leukotriene (LT) agent (FPL 55712), 5-lipoxygenase inhibitor (E6080), anti-allergic agent (azelastine), and anti-histamine agent (mepyramine maleate). We noted biphasic increase in NAR after antigen challenge; the first peak, 146.3 +/- 4.3% at 10 min and the second peak, 163.3 +/- 7.8% at 240 min after antigen challenge. The first peak response of NAR was not affected by anti-PAF agents, anti-LT agent, 5-lipoxygenase inhibitor, or azelastine; it was slightly but significantly inhibited by anti-histamine. The second NAR response was significantly inhibited by anti-PAF agents, anti-LT agent, 5-lipoxygenase inhibitor, and azelastine, but was not affected by anti-histamine. The nasal symptoms which occurred within 30 min after antigen challenge were significantly inhibited by WEB2086, E6080, azelastine, and mepyramine, but were not affected by SM10661. Our results suggest that PAF activities and LTs may play an important role in the later phase increase of NAR after topical antigen challenge.

Topics: Airway Resistance; Animals; Azepines; Chromones; Guinea Pigs; Histamine H1 Antagonists; Immunization; Lipoxygenase Inhibitors; Male; Ovalbumin; Phthalazines; Platelet Activating Factor; Pyrilamine; Rhinitis, Allergic, Perennial; Sneezing; SRS-A; Thiazoles; Thiazolidines; Triazoles