Antiallergic and anti-inflammatory effects of a novel I kappaB kinase beta inhibitor, IMD-0354, in a mouse model of allergic inflammation

Int Arch Allergy Immunol. 2009;148(3):186-98. doi: 10.1159/000161579. Epub 2008 Oct 10.


Background: Nuclear factor (NF)-kappaB is a transcription factor known to regulate allergy-associated cytokine and chemokine production related to the induction of inflammation. I kappaB kinase beta (IKK beta), which is responsible for activation of the NF-kappaB pathway, may be an ideal molecular target to inhibit this process. IMD-0354 [N-(3,5-bis-trifluoromethyl-phenyl)-5-chloro-2-hydroxy-benzamide] is an attractive novel IKK beta inhibitor that prevents the production of inflammatory cytokines in various diseases, although it is not known if IMD-0354 is effective against allergic inflammation. This study aimed to elucidate the antiallergic effects of a newly synthesized IKK beta inhibitor, IMD-0354, in a mouse model of allergic inflammation.

Methods: We generated ovalbumin (OVA)-sensitized mice which were then challenged with OVA. IMD-0354 was administered intraperitoneally to therapeutic groups. Lung histopathology and the concentrations of cytokines and chemokines in bronchoalveolar lavage fluid (BALF) and supernatants of lung homogenates were determined.

Results: Administration of IMD-0354 ameliorated airway hyperresponsiveness and reduced the numbers of bronchial eosinophils and mucus-producing cells in OVA-sensitized mice. The total numbers of cells and eosinophils in BALF were also reduced by treatment with IMD-0354. Treatment with IMD-0354 inhibited the production of Th2 cytokines such as interleukin (IL)-5 and IL-13 and eotaxin in the airways and/or lungs of OVA-sensitized mice, but it did not affect the restoration of Th1 cytokines such as IL-12 and interferon-gamma under the same experimental conditions. IgE production was also inhibited by IMD-0354.

Conclusion: A specific IKK beta inhibitor, IMD-0354, improved allergic airway inflammation and hyperresponsiveness in mice. IMD-0354 may have therapeutic potential for bronchial asthma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Airway Resistance / drug effects
  • Animals
  • Anti-Allergic Agents / pharmacology
  • Anti-Allergic Agents / therapeutic use*
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Benzamides / pharmacology
  • Benzamides / therapeutic use*
  • Body Weight / drug effects
  • Bronchoalveolar Lavage Fluid / chemistry
  • Bronchoalveolar Lavage Fluid / cytology
  • Cell Count
  • Chemokines / analysis
  • Chemokines / metabolism
  • Cytokines / analysis
  • Cytokines / metabolism
  • Disease Models, Animal
  • Eosinophils / cytology
  • Female
  • I-kappa B Kinase / antagonists & inhibitors*
  • I-kappa B Kinase / metabolism
  • Immunoglobulin E / blood
  • Immunoglobulin E / immunology
  • Lung / drug effects
  • Lung / metabolism
  • Lung / pathology
  • Lung / physiopathology
  • Lymphocytes / cytology
  • Macrophages / cytology
  • Mice
  • Mice, Inbred BALB C
  • Ovalbumin / administration & dosage
  • Ovalbumin / immunology
  • Respiratory Hypersensitivity / drug therapy*
  • Respiratory Hypersensitivity / pathology
  • Respiratory Hypersensitivity / physiopathology


  • Anti-Allergic Agents
  • Anti-Inflammatory Agents
  • Benzamides
  • Chemokines
  • Cytokines
  • Immunoglobulin E
  • N-(3,5-bis(trifluoromethyl)phenyl)-5-chloro-2-hydroxybenzamide
  • Ovalbumin
  • I-kappa B Kinase