Developing otitis media in experimental models

Abstract

Problem: The study investigated the early inflammatory changes in the TM in rat models of otitis media with effusion (OME), acute otitis media (AOM), and after degranulation of pars flaccida (PF) mast cells (MCs). Furthermore, we have developed a new model of AOM that resembles the natural route of infection in man. Methods: OME was initiated by blocking of the tympanal orifice of the Eustachian tube and AOM was initiated after inoculation of Streptococcus pneumoniae into the middle ear or nasal cavity. PF MCs were degranulated after local application of compound 48/80. The rats were followed-up with otomicroscopical examination. After the animals were euthanized, tympanic membranes (TMs) were dissected and embedded for (immuno-)histochemical examination. Results: OME and AOM elicited the first inflammatory response in the PF. The response to OME was discrete. During the first 48 hours of AOM the inflammatory response was intense, following a bimodal pattern. This reaction was similar to that found following MC degranulation. In AOM, macrophages predominated in PF, and polymorphonuclear cells in pars tensa. During early AOM fibrinogen/fibrin extravasated into the TM. In the new rat AOM model repeated nasal challenge with Streptococcus pneumoniae provoked AOM. Conclusion: The initial response to AOM is dependent on the activation of a nonspecific immune response that resembles that following degranulation of PF mast cells. In the OME model, the effusion may reflect a passive accumulation of fluid secreted from the normal mucosa. Fibrin deposited during early AOM may be involved in regulating the inflammatory response. Our new rat model of AOM minimizes trauma and is considered applicable to the development and testing of drugs in otitis media research. Significance: A future treatment strategy of otitis media may be transtympanic membrane treatment to modulate the early inflammatory response of the TM and middle ear cavity. Support: None reported.