Effect of TEI-9874, an inhibitor of immunoglobulin E production, on allergen-induced asthmatic model in rats.
As TEI-9874, 2-(4-(6-cyclohexyloxy-2-naphtyloxy)phenylacetamide)ben zoic acid reduces allergen-specific immunoglobulin E (IgE) production by human peripheral blood mononuclear cells in vitro, we evaluated its potency on an allergen-induced asthmatic model in Brown-Norway rats. Inhaled ovalbumin induced the immediate-phase asthmatic response, the late-phase asthmatic response, the infiltration of leukocytes into bronchoalveolar lavage fluid, and an increase of serum anti-ovalbumin IgE. These parameters were suppressed by the treatment with TEI-9874 (3, 10, and 30 mg/kg p.o.). The ovalbumin-induced airway hyperresponsiveness was prevented by TEI-9874 (30 mg/kg p.o.). Furthermore, the suppression of the immediate-phase asthmatic response and the late-phase asthmatic response by TEI-9874 was almost completely extinguished by the exogenous administration of rat anti-ovalbumin antiserum. These results indicate that the efficacy of TEI-9874 on the asthmatic response is mainly mediated by the suppression of allergen-specific IgE production and TEI-9874 appears to be a good candidate as therapy for IgE-mediated allergic asthma.
Nonaka
T
T
Teijin Institute for Bio-Medical Research, 4-3-2, Asahigaoka, Hino, 191-8512, Tokyo, Japan.
Mitsuhashi
H
H
Takahashi
K
K
Sugiyama
H
H
Kishimoto
T
T
D000485:Allergens / Q000494:pharmacology*; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology*; D001249:Asthma / Q000139:chemically induced / Q000517:prevention & control*; D044482:Benzeneacetamides; D001565:Benzoates / Q000494:pharmacology*; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000517:prevention & control; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D004797:Enzyme-Linked Immunosorbent Assay; D007073:Immunoglobulin E / Q000032:analysis / Q000096:biosynthesis*; D007074:Immunoglobulin G / Q000032:analysis / Q000096:biosynthesis; D007202:Indicators and Reagents; D016210:Methacholine Chloride / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology*; D010047:Ovalbumin / Q000276:immunology / Q000494:pharmacology; D051381:Rats; D011914:Rats, Inbred BN; D015656:Respiratory Mechanics / Q000187:drug effects
C416047:2-(4-(6-cyclohexyloxy-2-naphthyloxy)phenylacetamide)benzoic acid; D000485:Allergens; D018927:Anti-Asthmatic Agents; D044482:Benzeneacetamides; D001565:Benzoates; D007074:Immunoglobulin G; D007202:Indicators and Reagents; D009281:Naphthalenes; D016210:Methacholine Chloride; D007073:Immunoglobulin E; D010047:Ovalbumin