Experimental otitis media with effusion induced by intratympanic lipid A instillation.

Otitis media with effusion was induced in guinea pigs by intratympanic instillation of lipid A, the lipid moiety of gram-negative bacterial lipopolysaccharide from Salmonella minnesota Re595. Lipid A was chosen as an inducer because of its similar composition among various bacterial species. Animals were killed from the first to 14th day after instillation of various concentrations (0.2, 2, 20, 200 micrograms/ml) of lipid A in 0.5% triethylamine. By 3 days after instillation, all experimental animals developed serous middle ear effusion. The histologic findings included hemorrhage, mucosal edema, capillary engorgement, and migration of infiltrative cells including macrophages, polymorphonuclear neutrophils, and lymphocytes. These findings were most prominent 3 days after instillation, and the recovery of the middle ear epithelium was observed within 14 days. Repeated instillation of lipid A (2 micrograms/ml) at an interval of 14 days reinforced the local response accompanied by serous middle ear effusion. These findings indicate that lipid A can induce the inflammatory changes with middle ear effusion and that lipid A plays an important role in the pathogenesis of otitis media with effusion.