2052 Inhibition of Allergic Response By Intranasal Topical Selective Nuclear Factor-Kappa B Inhibitor in Murine Model of Allergic Rhinitis

Thursday, 15 October 2015
Hall D1 Foyer (Floor 3) (Coex Convention Center)

Jee Hye Wee , Otorhinolaryngology-Head and Neck Surgery, Seoul National University Bundang Hospital, Seongnam, South Korea

Yu-Lian Zhang , Otorhinolaryngology-Head and Neck Surgery, Seoul National University College of Medicine, Seoul, South Korea

Chae-Seo Rhee, MD, PhD , Otorhinolaryngology, Seoul National University Bundang Hospital, South Korea

Dong-Young Kim, MD, PhD , Seoul National University, Seoul, South Korea

Background: Study of murine asthma model revealed that specific local nuclear factor-kappa B (NF-kB) inhibition achieved using NF-kB decoy oligodeoxynucleotides (ODNs) had therapeutic potential in the control of pulmonary allergy. However, the questions of whether local inhibiting NF-kB could have therapeutic value in the treatment of allergic rhinitis (AR). The objective of this study was to evaluate the effect of selective NF-κB inhibition using NF-κB decoy ODNs for local treatment of AR in ovalbumin (OVA)-sensitized wild-type mice.
Methods: BALB/c mice were sensitized with OVA and alum and then challenged intranasally with OVA. NF-kB inhibitor, NF-kB decoy ODNs was given intranasally to the treatment group and NF-kB scrambled ODNs to the sham treatment group. Allergic symptom scores, eosinophil infiltration, the levels of cytokines in the nasal mucosa, nasal lavage fluid, and spleen cell culture, serum total and OVA-specific immunoglobulins, and intercellular adhesion molecure-1 (ICAM-1) in the nasal mucosa were analyzed.
Results: NF-κB decoy ODNs significantly reduced allergic symptoms and eosinophil infiltration in the nasal mucosa. It also suppressed serum level of total IgE, OVA-specific IgE and IgG1. The IL-5 and TNF-α level and the expression of ICAM-1 were decreased in the nasal mucosa of the treatment group when compared to the positive control and sham treatment groups. In addition, IL-6 significantly decreased in the nasal lavage fluid of treatment group. Furthermore, NF-κB decoy ODNs significantly reduced expression of systemic Th2 cytokine, IL-4 and IL-5 in the spleen cell culture.
Conclusion: This study demonstrates for the first time that local NF-κB inhibition using NF-κB decoy ODNs suppressed the allergic response in murine AR model. This shows a therapeutic potential of local NF-κB inhibition in the control of AR.