The Role of Soluble Interleukin-4 Receptor and Interleukin-5 Antibody in Preventing Late-Phase Allergy-Induced Eustachian Tube Dysfunction

Abstract

OBJECTIVES: We investigated the role of soluble interleukin (IL)-4 receptors (sIL-4R) and IL-5 antibodies (IL-5Ab) in preventing allergic eustachian tube dysfunction (ETD) and middle ear effusion (MEE). STUDY DESIGN: Brown-Norway rats were sensitized to ovalbumin (OVA) and challenged transtympanically. Two groups of rats received either IL-4R or IL-5Ab transtympanically 1 hour before challenge. Three additional groups were used as controls. Following the second transtympanic challenge, the ventilatory and clearance functions of the eustachian tube (ET) were assessed at 0, 2, and 8 hours. Histology was prepared using cut paraffin sections stained with hematoxylin and eosin. RESULTS: sIL-4R-pretreated rats showed no significant changes in ventilatory or clearance functions of the ET or inflammatory changes in ET mucosa, whereas IL-5Ab pretreatment showed significant late ventilatory and clearance dysfunction as well as inflammatory mucosal changes. CONCLUSION: These data demonstrate that the late-phase allergic inflammatory response that leads to subsequent formation of ETD and MEE is prevented by pretreatment with sIL-4R and, more modestly, with IL-5Ab. Otitis media with effusion (OME) remains a significant problem in the pediatric population today. Despite advances in screening and treatment, the incidence has steadily risen over the past 20 years. It is now estimated that more than 80% of all children with have at least 1 episode of OME by age 3 and 40% will have 3 or more episodes. 1 Furthermore, earaches/ear infections represent the single greatest reason for a visit to the pediatrician after well-child visits. 2 Numerous studies have investigated the sequelae for children exposed to multiple episodes of OME, with conclusions ranging from no significant permanent deficits to impairments in receptive language skills, 1 balance and coordination, 3 and school readiness measures. 4 There remain several important controversies with regards to the pathogenesis and treatment of OME. One of these is the relationship between OME and allergy. A link between OME and allergy has existed for some time, 5 and one of the older empiric observations on the relationship between children with recurrent OME and allergy has resurfaced in recent years to explain the large number of patients with no other causative factor for fluid in the middle ear space. Bernstein 6 has demonstrated in a study of 100 patients with recurrent OME that almost a third can be attributed directly to allergy. Indeed, some consider this number a very conservative estimate. It is the intent of this study to examine the role of newer therapies such as antagonists to interleukin (IL)-4 and IL-5 for preventing the late-phase allergic reaction and their effect of preventing eustachian tube dysfunction and formation of middle ear effusion. IL−4 and −5 are 2 of a host of mediators that comprise the late-phase allergic response. Produced by a variety of cell types, their principal functions are to control subsequent cascades that are a response to antigenic challenge. Tissue inflammation, edema formation, mucus production, and eosinophilia are controlled by these cytokines. Our hypothesis is that administration of antagonists of both IL−4 and IL−5, in the form of sIL-4R and IL−5Ab, respectively, will result in a decreased allergic response to challenged tissue.