ovalbumin and Otitis-Media

The objective of this study was to evaluate the effects of allergic rhinitis (AR) on the development, progression, and recovery of acute otitis media (OM) in an animal model and investigate the secondary effects of bacterial infection.. BALB/c mice were divided into four groups: AR + OM, AR, OM, and control groups. AR + OM and AR groups were sensitized with ovalbumin (OVA) and alum and then challenged intranasally with OVA. Phosphate-buffered saline (PBS) was administered to the OM and control groups the same number of times. After AR induction, OM was induced by surgical inoculation of non-typeable Haemophilus influenza (NTHi) into the middle ear (ME) cavity of the mice in the AR + OM and OM groups. PBS was injected into the bulla in the AR and control groups. Each group was subdivided into sets of six mice, one for each of the four time points (0, 2, 7, and 10 days post-bacterial inoculation), at which point the mice were euthanized and ME and nasal cavity mucosa were obtained and evaluated. The occurrence of OM and the ME mucosa thickness were evaluated and compared among the four groups. Tissue expression of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) in infected ME mucosa was assessed by immunohistochemical staining. We also investigated IgE, IL-4, and IL-5 in the nasal mucosa.. Most of the ears showed OM on post-inoculation day 2 in both AR + OM and OM groups. In the AR + OM group, 58.3% of ears still had OM on post-inoculation day 10, while only 16.7% of the OM group had OM. The ME mucosa of all groups increased, and the AR + OM group exhibited the thickest mucosa. The OM group showed peak thickness on post-inoculation day 2 and then decreased, whereas the ME mucosa thickness of the AR + OM group continued to increase to day 7. In the OM group, the expression of IL-1β, IL-6, and TNF-α in the ME also increased significantly, peaking on post-inoculation day 2, and then gradually decreased. In the AR + OM group, the expression of these proteins increased until day 7 and then decreased. The IgE and Th2 response (IL-4 and IL-5) cytokines were expressed at higher levels in the AR + OM and AR groups than in the OM and control groups.. The inflammatory reaction to NTHi was more intense and lasted longer in the allergic group, which indicates that AR affects the progression and subsequent recovery of acute bacterial OM.

Topics: Animals; Cytokines; Disease Models, Animal; Mice; Mice, Inbred BALB C; Nasal Mucosa; Otitis Media; Ovalbumin; Rhinitis, Allergic

Otitis media with effusion (OME) often occurs in infants and young children, which is related to allergic reactions. Notch signaling pathway plays an important role in allergic responses. In this study, we aimed to investigate the role of Notch signaling pathway in the ovalbumin (OVA)-mediated allergic OME in vivo. OVA-induced OME rats were treated with a control vehicle or a γ-secretase inhibitor, N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT) suppressing the Notch signaling. We studied the effect of Notch signaling pathway in OME model, including histopathological assessment, the expression of Th1 cytokines (IFN-γ), Th2 cytokines (IL-4, IL-5), key transcription factors (T-bet, GATA-3) by quantitative real-time polymerase chain reaction (qRT-PCR). In addition, the level of Notch ligand (Jagged1) and the downstream target gene Hes1 were also evaluated by qRT-PCR and immunofluorescent staining. We observed that the production of Th2 cytokines was increased, the level of Th1 cytokines was decreased in OME experimental model. Likewise, Th2-cytokine(IL-4)level was reduced, but the level of Th1 cytokines(IFN-γ) was no changes. Additionally, administration of DAPT induced a decrease in the expression of GATA-3 mRNA, however, no influence on T-bet mRNA production. These results suggest that there is an imbalance with Th1/Th2 in OVA-mediated allergic OME. DAPT treatment can block the Notch signaling pathway and relieve the middle ear inflammation through modulating the level of Th2 responses in OVA-induced allergic OME.

Topics: Allergens; Amyloid Precursor Protein Secretases; Animals; Anti-Inflammatory Agents; Cytokines; Diamines; GATA3 Transcription Factor; Jagged-1 Protein; Male; Otitis Media; Ovalbumin; Rats, Sprague-Dawley; Th2 Cells; Thiazoles; Transcription Factor HES-1

As the periods of intratympanic injection of ovalbumin (OVA) to the middle ear became longer, marked eosinophil infiltration in the perilymphatic space was observed. Moreover severe morphological damage of the organ of Corti was observed in the 28-day antigen-stimulation side. These results indicate that eosinophilic inflammation occurred in the inner ear and caused profound hearing loss.. The purpose of the present study was to elucidate the inner ear damage in a new animal model of eosinophilic otitis media (EOM) which we recently constructed.. We constructed the animal model of EOM by intraperitoneal and intratympanic injection of OVA. Infiltrating cells and the inner ear damage were examined by histological study.. In the inner ear, a few eosinophils were seen in the scala tympani of the organ of Corti and the dilation of capillaries of the stria vascularis was observed in the 7-day stimulation side. In the 14-day antigen stimulation side, some eosinophils and macrophages were seen in not only the scala tympani but also the scala vestibule. In the 28-day antigen-stimulation side, severe morphological damage of the organ of Corti and many eosinophils, red blood cells, and plasma cells infiltrating the perilymph were observed.

Topics: Animals; Cochlear Aqueduct; Disease Models, Animal; Ear, Inner; Ear, Middle; Eosinophilia; Eosinophils; Guinea Pigs; Injections; Injections, Intraperitoneal; Leukocyte Count; Macrophages; Organ of Corti; Otitis Media; Ovalbumin; Perilymph; Round Window, Ear; Scala Tympani; Stria Vascularis

New pathophysiologic concepts are needed to explain the clinically observed connection between the allergic diathesis and otitis media. Although mast cells, unlike lymphocytes, are common in the normal middle ear mucosa, their potential role in innate immunity of the middle ear and in the expression of inflammatory responses in that space to bacterial challenge, as opposed to allergy, has received relatively little attention.. In the current study, we examine the contributions of mast cells to the pathogenesis of bacterially induced inflammation in the middle ear and thus to otitis media.. Wild-type mice, mast cell-deficient mice, and mast cell-deficient mice whose mast cell populations were restored by transplantation of bone marrow-derived mast cells were challenged by using models of bacterial and allergic middle ear inflammation.. Our results indicate that mast cells account for a substantial proportion of the innate immune response to bacteria in the middle ear.. This mechanism may link responses to allergy and infection in the middle ear mucosa, and thus the mast cell may be a critical control element in the pathogenesis of otitis media.

Topics: Animals; Bone Marrow Cells; Cells, Cultured; Drug Combinations; Ear, Middle; Female; Haemophilus Infections; Haemophilus influenzae; Hypersensitivity; Injections; Mast Cells; Mice; Mice, Congenic; Mice, Mutant Strains; Otitis Media; Ovalbumin

Topics: Animals; Ear, Inner; Guinea Pigs; Hypersensitivity; Otitis Media; Ovalbumin; Proteus