ovalbumin and fexofenadine

Nasal obstruction is one of the most bothersome symptoms of allergic rhinitis (AR) affecting sleep-related quality of life in AR patients. Although several treatments were tested to control nasal obstruction, some patients with moderate to severe AR do not respond to current treatments, including the combined administration of different types of anti-allergic medicine. Thus, new options for AR treatment are needed. This study aimed to evaluate the effects of combined treatment with a novel inhibitor of hematopoietic prostaglandin D synthase (HPGDS), TAS-205, and different types of anti-allergic medicine on nasal obstruction in AR. Firstly, we demonstrated that TAS-205 selectively inhibited prostaglandin D

Topics: Acetates; Animals; Anti-Allergic Agents; Cell Line; Cyclopropanes; Disease Models, Animal; Drug Synergism; Drug Therapy, Combination; Enzyme Inhibitors; Guinea Pigs; Humans; Intramolecular Oxidoreductases; Lipocalins; Male; Morpholines; Nasal Mucosa; Nasal Obstruction; Ovalbumin; Piperidines; Prostaglandin D2; Pyrroles; Quality of Life; Quinolines; Rats; Rhinitis, Allergic; Sulfides; Terfenadine

Interleukin-16 (IL-16) is a cytokine that induces selective migration of CD4+ cells and participates in inflammatory diseases including allergic rhinitis. Histamine and prostaglandin D(2) are important chemical mediators of allergic inflammation, and antiallergic drugs are commonly used for the treatment of allergic rhinitis. It remains unknown whether treatment with the drugs affects IL-16.. We evaluated the variability of IL-16 and the effects of the antiallergic drugs fexofenadine (40 mg/kg/day) and ramatroban (30 mg/kg/day) on IL-16 in an OVA-sensitized BALB/c murine experimental allergic rhinitis model.. We measured the expression level of IL-16 protein in the mouse nasal septal mucosa by immunohistochemistry, and the serum level of IL-16 by ELISA. Several other parameters associated with allergic rhinitis (nasal symptoms, OVA-specific IgE, eosinophil and T cell infiltration) were also measured.. Local and systemic expressions of IL-16 were significantly increased in OVA-sensitized mice when compared to the nonsensitized group. Fexofenadine and ramatroban significantly inhibited the following OVA-induced allergic features when compared to the nontreated sensitized group: sneezing, nasal rubbing, eosinophil infiltration, IL-16 expressions in nasal tissue, and serum IL-16 level. Serum OVA-specific IgE and local T cell infiltration were reduced, but they did not reach significant values.. These results suggest that IL-16 was both systemically and locally upregulated in the murine allergic rhinitis model and that IL-16 changed in parallel to allergic state by treatment with the drugs.

Topics: Animals; Anti-Allergic Agents; Carbazoles; Disease Models, Animal; Eosinophils; Female; Immunoglobulin E; Interleukin-16; Mice; Mice, Inbred BALB C; Nasal Mucosa; Ovalbumin; Platelet Aggregation Inhibitors; Rhinitis, Allergic, Perennial; Sulfonamides; Terfenadine

Allergic rhinitis is an inflammatory disease of the nasal mucosa, induced by histamine, leukotrienes, and other substances released from mast cells. Fexofenadine hydrochloride, the active metabolite of terfenadine, is a novel, nonsedating antiallergic drug having H1 receptor antagonistic activity. Fexofenadine is effective for the treatment of allergic rhinitis. However, its mechanism of action in attenuating nasal congestion has not yet been elucidated. Therefore, we first examined the effects of fexofenadine on a guinea pig model of antigen-induced rhinitis. We also evaluated the effects of mepyramine, zafirlukast and ramatroban in this model; these drugs are an H1 receptor antagonist, a selective leukotriene antagonist and a selective thromboxane antagonist, respectively. Rhinitis was induced by ovalbumin (OVA) instillation into the nasal cavity of animals that had been sensitized by two earlier OVA injections (s.c. and i.p.). The nasal airway resistance was measured for 45 min after the challenge. Fexofenadine hydrochloride (20 mg/kg) and terfenadine (20 mg/kg) administered orally 70 min prior to the challenge significantly inhibited (fexofenadine, p < 0.001, terfenadine, p < 0.05) the increase in nasal airway resistance. Ramatroban (30 mg/kg) administered orally 60 min prior to the challenge also significantly inhibited (p < 0.05) the increase in nasal airway resistance. In contrast, mepyramine (3 mg/kg i.v.) and zafirlukast (3 mg/kg p.o.) failed to reduce the increase in nasal airway resistance. These results suggest that thromboxane may be involved in the increase in the nasal airway resistance in this model. Accordingly, fexofenadine may reduce the increase in nasal airway resistance by inhibiting the release of chemical mediators, including thromboxane, that are involved in the increase in nasal airway resistance in this model.

Topics: Airway Resistance; Animals; Anti-Allergic Agents; Area Under Curve; Carbazoles; Disease Models, Animal; Guinea Pigs; Indoles; Leukotrienes; Male; Ovalbumin; Phenylcarbamates; Pyrilamine; Rhinitis; Sulfonamides; Terfenadine; Thromboxanes; Tosyl Compounds

There is renewed interest in antihistamines for the treatment of allergic asthma. A growing body of literature has shown that the newer compounds can affect inflammatory cell accumulation and cytokine/chemokine production. In a murine model of allergen-induced airway inflammation and hyperresponsiveness, the ability of fexofenadine to affect these outcomes was tested in a primary sensitization and challenge model and after treatment of donor mice before the adoptive transfer of T cells into recipients receiving limited allergen exposure. Mice were sensitized and challenged with allergen (ovalbumin). Airway function after inhaled methacholine was monitored in parallel to the assessment of tissue and airway inflammation and cytokine production. In further experiments, lung T lymphocytes from sensitized/challenged donor mice were transferred into naive recipients before limited airway challenge with the allergen. Administration of fexofenadine before challenge but after sensitization was effective in preventing tissue eosinophilia and airway hyperresponsiveness. Moreover, the treatment of donor mice with fexofenadine before transfer of lung T cells effectively prevented airway hyperresponsiveness and eosinophilia in naive mice exposed to limited airway challenge. These data therefore support the potential for fexofenadine in the treatment of allergen-induced airway hyperresponsiveness and inflammation.

Topics: Administration, Inhalation; Adoptive Transfer; Allergens; Animals; Anti-Allergic Agents; Antibody Specificity; Bronchoalveolar Lavage Fluid; Bronchoconstrictor Agents; Cytokines; Disease Models, Animal; Dose-Response Relationship, Drug; Eosinophils; Female; Histamine H1 Antagonists; Immunoglobulin E; Injections, Intraperitoneal; Leukocyte Count; Methacholine Chloride; Mice; Mice, Inbred BALB C; Ovalbumin; Respiratory Hypersensitivity; Rhinitis, Allergic, Perennial; T-Lymphocytes; Terfenadine; Time Factors; Treatment Outcome