Endotoxin-induced otitis media with effusion in the mouse. Immunohistochemical analysis.

A model of endotoxin-induced otitis media with effusion was developed in healthy BALB/c mice. Endotoxin extracted from Salmonella typhimurium (10 micrograms/ml) was injected into the middle ear bulla transtympanically and the resultant inflammatory response was analyzed using immunohistochemical methods. Serous effusions were observed otoscopically and mucosal edema and infiltrate were studied histologically, both peaking at 3 days and essentially resolving by 7 days. However, persistence of a small area of inflammation in the round window niche was consistently present at 2 weeks. The specific cellular responses to endotoxin were analysed by histologic and immunohistologic examination of the murine temporal bone. We used antibodies to identify T-lymphocytes (anti-Lyt-1, -Lyt-2), macrophages and neutrophils (anti-Mac-1), and immunoglobulins (anti-IgA, -IgG, -IgM). In the mucosal/submucosal infiltrate Mac-1+ and Lyt-1+ cells peaked from days 1 to 3. Within the luminal effusion Mac-1+ and Lyt-1+ cells as well as diffuse (not cell-associated) IgG, IgM, and IgA staining were most prevalent from days 1 to 3, while IgG-bearing plasma cells formed the majority of the luminal cells observed at 1 to 2 weeks. No significant influx of T-suppressor cells was observed at any time. The round window niche and anterior portion of the tympanic bulla mucosa were found to be the most reactive areas. These results suggest that endotoxin alone is capable of producing an inflammatory infiltrate in the mouse consistent with otitis media with effusion, and that the interaction of endotoxin with resident immunocytes of the middle ear, as well as serum derived immune cells, is consistent with the known phlogistic properties of endotoxin.