1. ¹Laboratory of Veterinary Molecular Pathology and Therapeutics, Division of Animal Life Science, Graduate School, Institute of Symbiotic Science and Technology, Tokyo University of Agriculture and Technology, Tokyo, Japan
2. ²Institute of Medicinal Molecular Design Inc., Tokyo, Japan

Correspondence: Dr Hiroshi Matsuda, Laboratory of Veterinary Molecular Pathology and Therapeutics, Division of Animal Life Science, Graduate School, Institute of Symbiotic Science and Technology, Tokyo University of Agriculture and Technology, 3-8-5 Saiwai-cho, Fuchu, Tokyo 183-8509, Japan. E-mail: hiro@cc.tuat.ac.jp

Received 19 April 2006; Revised 24 July 2006; Accepted 28 August 2006; Published online 19 October 2006.

Abstract

Growing evidence has demonstrated the crucial role of NF-B activation on disease severity in allergic disorders. In this study, we examined the clinical relevance of a novel NF-B inhibitor, IMD-0354, for atopic dermatitis (AD) by its topical application. To investigate the in vivo efficacy, 1% IMD-0354 ointment was applied daily to NC/NgaTnd mice with severe dermatitis, which served as a model for human AD. During 2 weeks of treatment, scratching behavior decreased and severity of dermatitis reduced in mice treated with IMD-0354 as well as FK506 without diverse effects. Based on histological examinations, the hyperplasia of keratinocytes and infiltration of inflammatory cells were significantly reduced in the skin of IMD-0354-treated mice. The expressions of T-helper 2 cytokines and tumor necrosis factor- at the affected skin sites were downregulated in IMD-0354-treated mice. Furthermore, IMD-0354 suppressed the proliferation of various immunocompetent cells, neurite outgrowth of nerve growth factor-stimulated pheochromocytoma cells, IgE production from splenic B cells, and IgE-mediated activation of mast cells in vitro. IMD-0354 effectively reduced the allergic inflammation in NC/NgaTnd mice in vivo. Thus, a drug that interferes with NF-B activity may provide an alternative therapeutic strategy for the treatment of AD.