Prevention of acute allergic conjunctivitis and late-phase inflammation with immunostimulatory DNA sequences.
OBJECTIVE
To evaluate the therapeutic potential of immunostimulatory sequence oligodeoxynucleotides (ISS-ODN) administration in ocular allergy, using a mouse model of ragweed-specific conjunctivitis.


METHODS
A murine model of allergic conjunctivitis involving SWR/J mice sensitized and challenged with short ragweed was used to test immunostimulatory DNA sequences for therapeutic potential. ISS-ODN or control ODN (0.1 mg/mouse) was administered intraperitoneally or topically to the conjunctiva 3 days before final allergen challenge. Multiple parameters of clinical symptoms evident during the acute-phase reaction and the cellular components of the late-phase reaction were evaluated in both groups of mice.


RESULTS
All parameters of clinical symptoms were markedly inhibited after intraperitoneal injection of ISS-ODN, whereas topical application to the conjunctiva did not inhibit clinical symptoms significantly. Remarkably, a single topical treatment with ISS-ODN (as well as by intraperitoneal injection) completely inhibited both eosinophilia and neutrophilia in the late-phase reaction.


CONCLUSIONS
Systemic or conjunctival administration of ISS-ODN was shown to significantly inhibit allergic responses in this mouse model. This indicates that ISS-ODN may be an effective form of immunotherapy for this class of allergic disease.
Miyazaki
D
D
Schepens Eye Research Institute, Brigham and Women's Hospital and. Committee on Immunology, Harvard Medical School, Boston, Massachusetts, USA.
Liu
G
G
Clark
L
L
Ono
S J
SJ
D000208:Acute Disease; D000276:Adjuvants, Immunologic; D000287:Administration, Topical; D000485:Allergens / Q000009:adverse effects; D000818:Animals; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D003233:Conjunctivitis, Allergic / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D004247:DNA / Q000276:immunology*; D004802:Eosinophilia / Q000517:prevention & control; D004804:Eosinophils / Q000187:drug effects; D005260:Female; D006968:Hypersensitivity, Delayed / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D007274:Injections, Intraperitoneal; D051379:Mice; D009504:Neutrophils / Q000187:drug effects; D009838:Oligodeoxyribonucleotides / Q000276:immunology*; D013873:Thionucleotides / Q000276:immunology*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000627:therapeutic use*
D000276:Adjuvants, Immunologic; D000485:Allergens; D009838:Oligodeoxyribonucleotides; D013873:Thionucleotides; D019444:Vaccines, DNA; D004247:DNA