Immune modulatory oligonucleotides in prevention of nasal allergen-induced Eustachian tube dysfunction in rats.
OBJECTIVE
Develop a model of nasal allergen-induced Eustachian tube dysfunction (ETD) in a rat and investigate the role of immune modulatory oligonucleotides (IMOs) in the prevention of nasal allergen-induced ETD.


METHODS
Prospective, randomized study. Brown Norway rats were sensitized to ova albumin (OVA) and randomized to receive pretreatment with IMOs or phosphate-buffered saline. All animals were challenged intranasally with aerosolized OVA. Dynamic measures of Eustachian tube (ET) function were analyzed.


RESULTS
Animals that were OVA-sensitized and IMO-pretreated had significantly lower mean passive opening (95% confidence interval [95% CI] 15.0,19.4) and closing (95% CI 4.8,7.8) ET pressures compared with those of (95% CI 24.1,32.7) and (95% CI 12.1,18.8) OVA-sensitized untreated rats, respectively. In addition, the IMO-pretreated animals demonstrated the ability to actively clear a significantly higher proportion of negative pressure (95% CI 0.64,0.96) compared with the untreated animals (95% CI 0.09,0.39). IMO-pretreated animals also demonstrated significantly improved mean mucociliary clearance times in seconds (95% CI 115,195) than those in untreated animals (95% CI 308,668).


CONCLUSIONS
Pretreatment with IMOs prevented allergen-induced allergic inflammation around the Eustachian tube (ET) and resulted in improved ventilatory function of the ET compared with sensitized untreated animals. IMOs offer considerable promise in the management of nasal allergic disease as well as otitis media with effusion.
Department of Otolaryngology-Head and Neck Surgery, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA. cebert@med.unc.edu
Charles S
CS
Ebert
Austin S
AS
Rose
Deidra A
DA
Blanks
Rose P
RP
Eapen
Ekambar R
ER
Kandimalla
Sudhir
S
Agrawal
Jiri
J
Prazma
Harold C
HC
Pillsbury
D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D005064:Eustachian Tube / Q000276:immunology / Q000503:physiopathology*; D007155:Immunologic Factors / Q000494:pharmacology*; D007279:Injections, Subcutaneous; D008297:Male; D009841:Oligonucleotides / Q000494:pharmacology*; D010034:Otitis Media with Effusion / Q000139:chemically induced / Q000276:immunology / Q000503:physiopathology / Q000517:prevention & control*; D010047:Ovalbumin; D011446:Prospective Studies; D011897:Random Allocation; D051381:Rats; D011914:Rats, Inbred BN
D007155:Immunologic Factors; D009841:Oligonucleotides; D010047:Ovalbumin