ovalbumin and desloratadine

Allergic rhinitis (AR) is an IgE-mediated inflammation which causes olfactory dysfunction. Antihistamines have been widely used to treat AR while few studies have investigated the effect of antihistamines on improving the sense of smell. In addition, the underlying mechanisms are not well elucidated. We established the ovalbumin (OVA)-induced allergic rhinitis rat model and administrated desloratadine to AR rats. The AR symptoms, serum level of OVA-specific IgE and IL-17, and expression of IL-4, IL-5 and IL-13 in nasal mucosa were measured. The olfactory dysfunction was monitored by buried food test and the expression of GluR1 was measured. Desloratadine treatment alleviated AR symptoms, decreased serum level of OVA-specific IgE and IL-17 in AR rats. Desloratadine decreased IL-4, IL-5, and IL-13 expression in nasal mucosa of AR rats. Desloratadine ameliorated olfactory dysfunction in AR rats and decreased GluR1 expression in AR rats. Desloratadine treatment alleviated AR symptoms and ameliorated olfactory dysfunction in AR rats. The expression of AMPA receptor subunit GluR1 in olfactory bulb was associated with olfactory disorder.

Topics: Animals; Disease Models, Animal; Histamine H1 Antagonists, Non-Sedating; Immunoglobulin E; Interleukins; Loratadine; Nasal Mucosa; Olfaction Disorders; Olfactory Bulb; Ovalbumin; Rats; Rats, Sprague-Dawley; Receptors, AMPA; Rhinitis, Allergic

Desloratadine is a biologically active metabolite of loratadine which is indicated for the treatment of allergic rhinitis. Bosentan is a dual endothelin receptor antagonist used to treatment of pulmonary artery hypertension (PAH). In this study, we aimed to determine the role of endothelins in allergic rhinitis (AR) and the effects of endothelin receptor antagonists in AR rat models through comparison with desloratadine.. In total, 20 adult Sprague-Dawley rats were used in this study. An ovalbumin-induced allergic rhinitis model was formed in three study groups except for the control group. Bosentan (100 mg/kg/day) was given to the bosentan-treated group for 7 days and desloratadine (10 mg/kg/day) was administered to the antihistaminic-treated group for 7 days. Nasal symptom scorings and histopathological examinations of the nasal tissues were carried out. Serum IgE levels and ET-1 and TNF-alpha mRNA expression levels were analysed. Between group comparisons for nasal symptoms, histopathological analysis, and molecular analyses were performed with a one-way ANOVA and Duncans multiple comparison tests. Significance was accepted at p smaller than 0.05.. Bosentan inhibited nasal symptom more significantly than desloratadine. The IgE level, ET-1 and TNF-alpha mRNA expression levels statistically increased in the allergic rhinitis group when compared to other groups. Conversely, the bosentan-treatment group showed a significant recovery from the same parameters. The deterioration in histopathological parameters reached the highest levels in the allergic rhinitis group. The histopathological findings were close to those of the control group in the bosentan and antihistaminic-treated group.. ET-1 is one of the mediators that impact AR development and ET-1 antagonists can be useful for symptom control and for decreasing allergic inflammation in AR patients.

Topics: Animals; Bosentan; Disease Models, Animal; Down-Regulation; Endothelin Receptor Antagonists; Endothelin-1; Female; Immunoglobulin E; Loratadine; Ovalbumin; Rats, Sprague-Dawley; Rhinitis, Allergic; RNA, Messenger; Sulfonamides; Tumor Necrosis Factor-alpha

Allergic rhinitis (AR) is a very common worldwide problem; patients display a number of symptoms, such as sneezing, nasal itching, and rhinorrhea, and their lifestyle is affected. Desloratadine is a novel, long-acting inhibitor of histamine. However, very little is known about the effect of desloratadine citrate disodium injection (DLC injection) on AR, and the underlying mechanisms are yet unexplored. Herein, we sought to explore the effects and mechanisms of actions of DLC injection in ovalbumin (OVA)-induced immune responses in a rat model of AR.. Sixty rats were subjected to immunization with OVA (intraperitoneal [i.p.]), followed by a nasal challenge with OVA. Drugs or saline were given daily for treatment. Nasal symptoms and histology of the nasal mucosa were examined. Cytokines such as interleukin (IL)-4, IL-12, interferon (IFN)-γ, adhesion molecules such as soluble vascular cell adhesion molecule 1 (sVCAM-1), and inducible nitric oxide synthase (iNOS) expression were assessed by enzyme-linked immunosorbent assay (ELISA) kit. Nitric oxide (NO) concentration was also measured by NO assay kit.. DLC treatment (intravenous [i.v.]) significantly decreased the frequency of sneezing and nasal scratching and alleviated nasal inflammation by increasing the serum levels of IFN-γ and IL-12, while lowering the expression of IL-4. Thus, DLC (i.v.) treatment led to a marked elevation in T-helper 1/T-helper 2 (Th1/Th2) ratio when administered in the AR rats. The expression of sVCAM-1, iNOS, and NO were also reversed.. DLC (i.v.), given after an allergen challenge, improved Th1 cytokines level and restrained Th2 responses alleviating the symptoms of AR. Our results indicate that DLC injection may exhibit such effects through the modulation of T-cell responses.

Topics: Allergens; Animals; Cell Adhesion Molecules; Citrates; Cytokines; Disease Models, Animal; Gene Expression Regulation; Histamine Antagonists; Humans; Immunomodulation; Loratadine; Nitric Oxide Synthase Type II; Ovalbumin; Rats; Rhinitis, Allergic; Sodium Citrate; T-Lymphocytes; Th1-Th2 Balance

Chemokines have chemotactic properties on leukocyte subsets whose modulation plays a pivotal role in allergic inflammatory processes. Our present study was designed to investigate the anti-allergic and anti-inflammatory properties of desloratadine citrate disodium injection (DLC) and elucidate the molecular mechanisms of its anti-inflammatory properties. The anti-allergic effects of DLC were evaluated based on allergic symptoms, serological marker production and histological changes of the nasal mucosa in guinea pigs model of allergic rhinitis. The anti-inflammatory properties and molecular mechanisms of DLC were explored by studying the regulation of a set of chemokines and extracellular signal-regulated kinase (ERK)1/2 and nuclear factor-kappa B (NF-κB) pathways, after DLC treatment in guinea pigs model of allergic rhinitis in vivo and histamine-activated human nasal epithelial cells (HNECs) in vitro. In vivo model in guinea pigs, DLC alleviated the rhinitis symptoms, inhibited inflammatory cells infiltration in nasal lavage fluid (NLF) and histamine, monocyte chemotactic protein (MCP)-1, regulated on activation normal T cell expressed, and presumably secreted (RANTEs) and interleukin (IL)-8 release in sera and P-ERK1/2 and NF-κB activation in nasal mucosa. In vitro, DLC markedly inhibited histamine-induced production of MCP-1, RANTEs and IL-8 and suppressed c-Raf, mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK) and ERK1/2 activation in HNECs. These results provide evidence that DLC possesses potent anti-allergic and anti-inflammatory properties. The mechanism of action underlying DLC in allergic inflammation appears to be inhibition of the phosphorylation of ERK1/2, in addition to blocking of the NF-κB pathway.

Topics: Animals; Anti-Allergic Agents; Cells, Cultured; Chemokine CCL2; Chemokine CCL5; Chemokines; Disease Models, Animal; Epithelial Cells; Extracellular Signal-Regulated MAP Kinases; Guinea Pigs; Histamine; Histamine H1 Antagonists; Humans; Injections; Interleukin-8; Loratadine; Nasal Lavage Fluid; Nasal Mucosa; NF-kappa B; Ovalbumin; Rhinitis, Allergic; Signal Transduction

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

To develop a physiologic test of nasal responsiveness in mice and to evaluate whether mice with acute bacterial sinusitis develop nasal hyperresponsiveness.. Several experimental studies will be described. The first was a titration pilot study. The second was a randomized, placebo-controlled study. The remainder were before-and-after trials. SPECIES: BALB/c or C57BL/6 mice.. For these experiments, we exposed mice to histamine intranasally, then counted the number of sneezes and nose rubs as the primary outcome measure of nasal responsiveness. First, we constructed a dose-response curve. Second, we treated the mice with desloratadine, a histamine 1 receptor antagonist, prior to histamine exposure. Third, we challenged, with intranasal histamine, mice made allergic using 2 techniques. Fourth, we infected mice with Streptococcus pneumoniae to determine whether acute sinusitis causes nasal hyperresponsiveness to histamine exposure.. Nasal histamine challenge led to a reproducible, dose-dependent increase in sneezing and nose rubs. The response to histamine exposure was blocked by desloratadine (P < or = .05). Allergic mice had a significant increase in responsiveness (P < or = .05) over baseline after exposure to antigen. Mice with acute sinusitis had a sustained increase in responsiveness, although less severe than after allergy, compared with baseline values that lasted 12 days after infection (P < or = .05).. Nasal challenge with histamine is a physiologic test of nasal responsiveness. The hyperresponsiveness of allergic mice to histamine exposure parallels the response to nonspecific stimuli during the human allergic reaction. In addition, we showed that acute bacterial sinusitis causes nasal hyperresponsiveness in mice.

Topics: Acute Disease; Animals; Dose-Response Relationship, Drug; Histamine; Histamine H1 Antagonists, Non-Sedating; Loratadine; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Nasal Mucosa; Ovalbumin; Rhinitis; Sinusitis; Stem Cells; Streptococcus pneumoniae

Histamine-1-receptor (H1R)-antagonists were shown to influence various immunological functions on different cell types and may thus be employed for immune-modulating strategies for the prevention of primary immune responses.. The aim of this study was to investigate the effects of an H1R-antagonist on allergen-induced sensitization, airway inflammation (AI) and airway hyper-reactivity (AHR) in a murine model.. BALB/c mice were systemically sensitized with ovalbumin (OVA) (six times, days 1-14) and challenged with aerosolized allergen (days 28-30). One day prior to the first and 2 h prior to every following sensitization, mice received either 1 or 0.01 microg of desloratadine (DL) or placebo per os.. Sensitization with OVA significantly increased specific and total IgE and IgG1 serum levels, as well as in vitro IL-5 and IL-4 production by spleen and peribronchial lymph node (PBLN) cells. Sensitized and challenged mice showed a marked eosinophilic infiltration in broncho-alveolar lavage fluids and lung tissues, and developed in vivo AHR to inhaled methacholine. Oral treatment with DL prior to OVA sensitization significantly decreased production of OVA-specific IgG1, as well as in vitro Th2-cytokine production by spleen and PBLN cells, compared with OVA-sensitized mice. Moreover, eosinophilic inflammation and development of in vivo AHR were significantly reduced in DL-treated mice, compared with sensitized controls.. Treatment with H1R-anatagonist prior to and during sensitization suppressed allergen-induced Th2 responses, as well as development of eosinophilic AI and AHR. This underscores an important immune modulating function of histamine, and implies a potential role of H1R-anatagonists in preventive strategies against allergic diseases.

Topics: Administration, Oral; Allergens; Animals; Bronchial Hyperreactivity; Cells, Cultured; Female; Histamine H1 Antagonists; Hypersensitivity; Immunoglobulin E; Immunoglobulin G; Interleukin-4; Interleukin-5; Loratadine; Lung; Lymph Nodes; Mice; Mice, Inbred BALB C; Models, Animal; Ovalbumin; Spleen

Histamine elicits many features of immediate hypersensitivity reactions. Recent evidence indicates that H1 receptors modulate immune responses to antigens. Desloratadine (DL), a new, long-acting, H1 receptor antagonist, has both a potent antihistaminic function and anti-inflammatory properties.. We sought to evaluate the effect of DL on allergic-airway responses in mice after inhalation of the naturally occurring aeroallergen Aspergillus fumigatus (Af ) and to examine the effects of DL on specific immune responses to a defined protein antigen with the use of an ovalbumin (OVA) model of asthma.. Mice were subjected either to repeated, intranasal application of Af extract or to intraperitoneal immunization with OVA, followed by inhalation challenge. DL or a control fluid was given daily throughout the sensitization process. Immunoglobulin E (IgE) levels, bronchoalveolar lavage-fluid cytokines and cytology, lung histology, and physiologic responses to methacholine were assessed in the allergen-treated mice. Anti-OVA IgE responses and OVA-driven T-cell cytokine production were examined.. Treatment with DL did not impair IgE production but did inhibit bronchial inflammation and bronchial hyperresponsiveness in both Af- and OVA-treated mice. This inhibition required that DL be administered concurrently with allergen sensitization, indicating that the attenuation of bronchial hyperresponsiveness and inflammation was not caused by anticholinergic receptor effects. OVA-responsive T cells from DL-treated mice exhibited depressed production of IL-4, IL-5, and IL-13 and normal amounts of interferon-gamma. The amounts of IL-5 and IL-13 were also diminished in the bronchoalveolar lavage fluid.. DL, given at the time of exposure to the allergen, inhibits T(H)2 responses, the induction of allergic pulmonary inflammation, and bronchial hyperresponsiveness. These results suggest that DL or similar agents given during times of antigen exposure might alter disease progression in patients with respiratory allergy.

Topics: Allergens; Animals; Asthma; Bronchial Hyperreactivity; Cytokines; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Histamine H1 Antagonists, Non-Sedating; Immunoglobulin E; Inflammation; Loratadine; Mice; Mice, Inbred BALB C; Ovalbumin; Receptors, Histamine H1; T-Lymphocytes