Abstract 49 Allergy, Immunology, and Rheumatology Poster Symposium, Sunday, 5/2

Episodes of otitis media (OM) are frequently preceded by upper respiratory infections (URIs) with viral pathogens, including respiratory syncytial virus (RSV). A potential mechanism by which viral URIs predispose to the development of OM is via the local elaboration of pro-inflammatory cytokines. The purpose of this study was to determine whether there is an association between local levels of proinflammatory cytokines and the development of nasal/otologic symptomatology and pathophysiology during experimental RSV infection. In this study, 15 healthy adults were intranasally inoculated with a safety-tested strain of RSV. Daily assessments of nasal, throat and general symptom scores, nasal secretion weights, nasal conductance by rhinomanometry, eustachian tube function by sonotubometry, and middle ear pressures by tympanometry were performed before (day 0) and after (days 1-8) inoculation. Daily nasal lavages were also obtained and assayed for levels IL-1, IL-6, IL-8 and TNFalpha by ELISA. Ten subjects were infected as evidenced by viral shedding and/or seroconversion. During infection, symptom scores and nasal secretion weights were increased, and nasal conductance, eustachian tube function, and middle ear pressures were decreased. In general, changes in these parameters peaked on days 4-6. Local levels of IL-6 and IL-8, but not IL-1 and TNFalpha, were elevated during infection. Mean (±SEM) levels of IL-6 (pg/ml) and IL-8 (ng/ml) were 3.4 ± 2.1 and 0.6 ± 0.2 at day 0, 17.4 ± 6.9 and 0.7 ± 0.2 at day 2, 14.5 ± 4.4 and 3.3 ± 2.8 at day 4, 4.6 ± 2.8 and 3.6 ± 2.1 at day 6, and 0 ± 0 and 2.6 ± 1.0 at day 8, respectively. These results demonstrate a temporal relationship between local elevations of certain pro-inflammatory cytokines and the development of nasal/otologic pathophysiology during experimental infection with RSV and suggest that, in susceptible individuals, the local elaboration of these cytokines during viral URIs may contribute to the development of OM. A better understanding of these cytokine responses could result in the elucidation of the mechanism by which viral URIs predispose to the development of OM and may result in the development of novel therapies for the treatment or prevention of this disorder.

This study was funded by NIH AI19262 and M01RR0084.