Tumor necrosis factor during experimental lipopolysaccharide-induced otitis media

Studies in our laboratory and others have indicated that endotoxin is present in a high percentage of human middle ear effusions, including those that are culture negative. Endotoxin has been identified as one of the most potent inducers of tumor necrosis factor (TNF), but this relationship has not been investigated in regard to the pathogenesis of otitis media, The purpose of this study was to determine whether endotoxin induces the production of TNF in the middle ear. Otitis media was induced in chinchillas by the injection of isolated lipopolysaccharide and middle ear fluids (MEFs) and serum harvested and assayed for TNF content by means of a cytolytic assay using L-929 cells and the Cell Titer 96 assay (Promega, Madison, WI). The MEF pools' TNF concentration ranged from 200 to 1,100 pg/mL MEF. Serum pools did not contain any detectable TNF. The results of the present study suggest that endotoxin induces TNF production locally in the middle ear cleft, which may contribute to the pathogenesis of otitis media via any number of established inflammatory pathways.