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Middle ear fluid lysozyme source in experimental pneumococcal otitis media
N Nonomura1, G S Giebink, D Zelterman
1Department of Otolaryngology, School of Medicine, University of Minnesota, Minneapolis.
Abstract:
Middle ear infection with Streptococcus pneumoniae is important in the pathogenesis of acute and chronic otitis media, and lysozyme in middle ear fluid (MEF) is an important inflammatory mediator in this disease. To determine the source of lysozyme during the early period of acute pneumococcal otitis media, chinchillas were irradiated to induce neutropenia, and their middle ears were inoculated with heat-killed, encapsulated pneumococci. The number of inflammatory cells and concentration of lysozyme were measured in MEF between 6 and 72 hours after inoculation. In pneumococcus-inoculated ears, the mean number of inflammatory cells but not lysozyme was significantly lower in MEF from irradiated animals than that from nonirradiated animals at 6 hours. Since lysozyme accumulated in MEF before the influx of inflammatory cells in irradiated animals, the initial release of this inflammatory mediator is most likely not from inflammatory cells; and mucosal epithelial cells, the only other known source of lysozyme in the middle ear environment, were the probable source induced by the direct stimulation of pneumococci. Inflammatory cells may contribute lysozyme later in the inflammatory response, since cellular and lysozyme concentrations in irradiated and nonirradiated animals were similar between 24 and 72 hours. These results suggest that future therapeutic interventions to limit middle ear inflammation in acute otitis media may need to recognize the direct action of pneumococcal cells or their envelope components on middle ear epithelium.
Insights
In acute otitis media, Streptococcus pneumoniae directly stimulates middle ear epithelial cells to release lysozyme, an inflammatory mediator. This occurs before inflammatory cells arrive, suggesting a new therapeutic target.
Area of Science:
- Otorhinolaryngology
- Microbiology
- Immunology
Background:
- Middle ear infections caused by Streptococcus pneumoniae are a major factor in acute and chronic otitis media.
- Lysozyme in middle ear fluid (MEF) is a key inflammatory mediator in this condition.
Purpose of the Study:
- To identify the source of lysozyme during the early stages of acute pneumococcal otitis media.
Main Methods:
- Chinchillas were rendered neutropenic via irradiation.
- Middle ears were inoculated with heat-killed Streptococcus pneumoniae.
- Inflammatory cell counts and lysozyme concentrations in MEF were measured over 72 hours.
Main Results:
- Lysozyme levels in MEF increased before inflammatory cells appeared in neutropenic animals.
- Inflammatory cell numbers were significantly lower in neutropenic animals at 6 hours post-inoculation.
- Lysozyme and cell concentrations became similar in neutropenic and non-neutropenic animals between 24 and 72 hours.
Conclusions:
- Middle ear mucosal epithelial cells, not inflammatory cells, are the likely initial source of lysozyme in acute pneumococcal otitis media.
- Pneumococci or their components directly stimulate epithelial cells to release lysozyme.
- Future therapies for otitis media should consider the direct impact of pneumococci on middle ear epithelium.