Osteoarthritis (OA) is characterized by articular cartilage degradation and hypertrophic joint changes. Interleukin (IL)-18 is a potent inducer of prostaglandin (PG) E2 in vitro. We determined the relation between IL-18 and PGE2 in synovial fluid (SF) of human OA, and discussed the role of IL-18 in the pathogenesis of OA and also its therapeutic consequences. SF was collected from 30 patients with knee OA. The concentrations of IL-18 and other cytokines including IL-1beta, tumor necrosis factor (TNF)-alpha, IL-6, and IL-8 were measured by enzyme-linked immunosorbent assay (ELISA). The concentration of PGE2 was also assessed by inhibitory ELISA. The average value of IL-18 was 248 +/- 310 pg/mL. The average value of PGE2 was 93 +/- 103 pg/mL. There was a relatively strong correlation between IL-18 and PGE2 (r = 0.78, p = 0.0001). In contrast, IL-1beta was undetectable (cutoff point of 20 pg/mL), except for one case. TNF-alpha was also undetectable (cutoff point of 20 pg/mL), except for two cases. The average value of IL-6 was 1,310 +/- 2,623 pg/mL (n = 17), whereas IL-8 was 5,208 +/- 6,031 pg/mL (n = 5). Furthermore, IL-6 and IL-8 correlated with IL-18 (r = 0.69, p = 0.0024 and r = 0.87, p = 0.0527, respectively). Our results suggest that IL-18 could play a major role in vivo in inducing the production of PGE2, which in turn can cause cartilage degradation in OA pathogenesis. Thus, targeting this cytokine appears to be an important therapeutic approach in OA.