Effect of TEI-9874, an inhibitor of immunoglobulin E production, on allergen-induced asthmatic model in rats

Eur J Pharmacol. 2000 Aug 25;402(3):287-95. doi: 10.1016/s0014-2999(00)00530-6.

Abstract

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.

MeSH terms

  • Allergens / pharmacology*
  • Animals
  • Anti-Asthmatic Agents / pharmacology*
  • Asthma / chemically induced
  • Asthma / prevention & control*
  • Benzeneacetamides*
  • Benzoates / pharmacology*
  • Bronchial Hyperreactivity / chemically induced
  • Bronchial Hyperreactivity / prevention & control
  • Bronchoalveolar Lavage Fluid / cytology
  • Enzyme-Linked Immunosorbent Assay
  • Immunoglobulin E / analysis
  • Immunoglobulin E / biosynthesis*
  • Immunoglobulin G / analysis
  • Immunoglobulin G / biosynthesis
  • Indicators and Reagents
  • Methacholine Chloride / pharmacology
  • Naphthalenes / pharmacology*
  • Ovalbumin / immunology
  • Ovalbumin / pharmacology
  • Rats
  • Rats, Inbred BN
  • Respiratory Mechanics / drug effects

Substances

  • 2-(4-(6-cyclohexyloxy-2-naphthyloxy)phenylacetamide)benzoic acid
  • Allergens
  • Anti-Asthmatic Agents
  • Benzeneacetamides
  • Benzoates
  • Immunoglobulin G
  • Indicators and Reagents
  • Naphthalenes
  • Methacholine Chloride
  • Immunoglobulin E
  • Ovalbumin