Monkey Model for IgE-Mediated Otitis Media with Effusion

Abstract

Allergic and other immune mechanisms have been suggested as important in the etiology and pathogenesis of OME, and both humoral and cellular components of the immune response have been identified in MEEs obtained from patients with OME. Yet, specific and direct documentation of an immune basis for OME has not been forthcoming. To establish a causal relationship between an immune hypersensitivity and middle ear pathophysiology, a provocative intranasal antigen challenge test has been designed using the nine-step inflation-deflation tympanometric test for ET dysfunction. These initial studies were undertaken by OMRC personnel in association with the allergy and immunology service. Subsequently, on the basis of the preliminary observations additional funding was obtained (NIAID AI 19262) to confirm and extend these studies to document antigen-induced ET dysfunction in allergic adults and children, and to establish a clinical relevance for antigen-induced ET dysfunction. Because questions concerning the etiology and pathogenesis required invasive techniques and are not suitable in humans, a monkey animal model has also been developed.

Our future plans will be to further develop the monkey model of OME employing IgE and other immune reactions in monkeys with normal ET function, or with compromised, surgically created ET function. The experimental MEE will be assayed for immune components, including IgA and its secretory piece; IgG, IgM, and IgE, total complement; C3, C4, and cells including polymorphonuclear leukocytes, eosinophils, and lymphocytes (both T and B cells). Since OME is mainly a disease of the young child, it is essential that age-related differences be explored in each aspect of our experimental model. The reversal and prevention of ET dysfunction and/or OME with several drugs, including cromolyn, steroids, and antihistamines, will be studied in humans and in the monkey model.