OBJECTIVE: Osteoarthritis (OA) in the TMJ is characterized by deterioration of articular cartilage and secondary inflammatory changes. Interleukin-1beta (IL-1beta) stimulates IL-6, IL-8, and vascular endothelial growth factor (VEGF) in synovial fluid of TMJ with internal derangement and bony changes. The cranberry (Vaccinium macrocarpon) contains polyphenolic compounds that inhibit production of pro-inflammatory molecules by gingival cells in response to several stimulators. This study examined effects of cranberry components on IL-1beta-stimulated IL-6, IL-8, and VEGF production by human TMJ synovial fibroblast-like cells. DESIGN: Cranberry high molecular weight non-dialyzable material (NDM) was derived from cranberry juice. Human TMJ synovial fibroblast-like cells from joints with degenerative OA and an ankylosed TMJ without degeneration were incubated with IL-1beta (0.001-1nM)+/-NDM (25-250mug/ml) (2h preincubation). Viability was assessed via activity of a mitochondrial enzyme. IL-6, IL-8, and VEGF in culture supernatants were measured by ELISA; NF-kappaB and AP-1 transcription factors were measured in nuclear extracts via binding to specific oligonucleotides. DATA ANALYSIS: ANOVA and Scheffe's F procedure for post hoc comparisons. RESULTS: NDM did not affect cell viability but inhibited IL-1beta stimulated IL-6, IL-8, and VEGF production in all cell lines (p0.05). NDM partially reduced nuclear levels of NF-kappaB and AP-1 (p0.04), depending upon cell line and time of exposure to IL-1beta+NDM. CONCLUSION: Cranberry NDM inhibition of IL-1beta-stimulated IL- 6, IL-8, and VEGF production by TMJ synovial fibroblast-like cells suggests that cranberry components may be useful as a host modulatory therapeutic agent to prevent or treat inflammatory arthropathies of the TMJ.