Immune modulatory oligonucleotides in prevention of nasal allergen-induced Eustachian tube dysfunction in rats.

Abstract

OBJECTIVES:

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.

STUDY DESIGN AND SETTING:

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.

• Authors: Charles S Ebert Jr, Austin S Rose, Deidra A Blanks, Rose P Eapen, Ekambar R Kandimalla, Sudhir Agrawal, Jiri Prazma, Harold C Pillsbury 3rd
• Journal: Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery (Otolaryngol Head Neck Surg) Vol. 137 Issue 2 Pg. 250-5 (Aug 2007) ISSN: 0194-5998 [Print] England
• PMID: 17666251 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Immunologic Factors
• Oligonucleotides
• Ovalbumin

Topics

• Analysis of Variance
• Animals
• Disease Models, Animal
• Eustachian Tube (immunology, physiopathology)
• Immunologic Factors (pharmacology)
• Injections, Subcutaneous
• Male
• Oligonucleotides (pharmacology)
• Otitis Media with Effusion (chemically induced, immunology, physiopathology, prevention & control)
• Ovalbumin
• Prospective Studies
• Random Allocation
• Rats
• Rats, Inbred BN