Allergen-independent immunostimulatory sequence oligodeoxynucleotide therapy attenuates experimental allergic rhinitis.
While effective for the prevention and treatment of allergic rhinitis (AR) symptoms, currently available medications do not reverse allergen specific hypersensitivities. Therefore, pharmacotherapeutics are not curative and their daily use is often required for years. These investigations were conducted to determine whether immunostimulatory sequence oligodeoxynucleotide (ISS-ODN) delivery protects previously sensitized mice from AR hypersensitivity responses and modulates their allergen specific immune profiles. Mice were first sensitized with ovalbumin (OVA) and alum, twenty-four hr before beginning a series of seven daily intranasal (i.n.) allergen challenges, subsets of mice received a single i.n. or intradermal (i.d.) dose of ISS-ODN or control oligodeoxynucleotide (C-ODN), a single intraperitoneal (i.p.) injection of dexamethasone (DXM), or no intervention. Mice receiving i.d. or i.n. ISS-ODN were found to have attenuated immediate and late phase effector cell responses to i.n. OVA challenge. Specifically, ISS-ODN treated mice had less histamine and cysteinyl leukotriene release and eosinophilic inflammation in their nasal passages than mice treated with C-ODN. In addition, splenocytes from ISS-ODN but not C-ODN treated mice displayed attenuated OVA-specific interleukin (IL)-4, IL-5, and IL-13 but increased interferon-gamma responses. Finally, ISS-ODN was generally a more effective treatment than DXM, both in blunting AR hypersensitivity responses and in shifting T helper 2 Th2-biased immune parameters towards Th1 dominance. As ISS-ODN delivery rapidly attenuated effector cell responses in this AR model in an allergen independent manner, the present results suggest that therapy with ISS-ODN alone may be an effective alternative to corticosteroid medications for the clinical management of AR.
Rhee
Chae-Seo
CS
Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University Hospital, Korea.
Libet
Lev
L
Chisholm
Dugald
D
Takabayashi
Kenji
K
Baird
Stephen
S
Bigby
Timothy D
TD
Lee
Chul Hee
CH
Horner
Anthony A
AA
Raz
Eyal
E
D000281:Administration, Intranasal; D000485:Allergens / Q000276:immunology; D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009838:Oligodeoxyribonucleotides / Q000276:immunology*; D010047:Ovalbumin / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D012220:Rhinitis / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D018418:Th2 Cells / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology
D000485:Allergens; D016207:Cytokines; D009838:Oligodeoxyribonucleotides; D019444:Vaccines, DNA; D010047:Ovalbumin