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OBJECTIVE:Xylitol is a natural sugar known to reduce dental decay. Recently, several epidemiology studies have also shown that xylitol can prevent acute otitis media in children. It is assumed that these effects are related to the inhibition of bacterial growth in the nasopharynx. However, the effects and safety of xylitol in middle ear epithelial cells, which play a key role in otitis media, have not been investigated. The present study was performed to investigate whether xylitol shows antiinflammatory or antioxidative effects on human middle ear epithelial cells and to assess its safety profile for clinical use. MATERIALS and METHODS:We induced inflammation in human middle ear epithelial cells (HMEEC) with lipopolysaccharide (LPS). After xylitol treatment, we measured expression levels of the inflammatory cytokines TNF-α and COX-2 and the mucin gene MUC5AC using semiquantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot analysis. Cell viability and morphological changes following xylitol treatment were investigated by 3-(4.5-dimethylthiazol-2-yl)-2.5-diphenyltetrazolium bromide (MMT) assay, flow cytometry, and Hoechst 33342 staining in human middle ear epithelial cells and mouse inner ear cells. RESULTS:Inflammatory cytokines and mucin gene expression were unaffected by xylitol. In addition, xylitol showed neither antioxidative effects nor cytotoxicity and did not stimulate apoptosis or necrosis of human middle ear epithelial cells or inner ear cells, even at high doses. CONCLUSION:Xylitol did not show antiinflammatory or antioxidative effects on HMMEC. It showed no toxicity in middle ear and inner ear cells. Xylitol may therefore be used safely to prevent acute otitis media.