It has been reported that nurse-like cells (NLCs) play a critical role in the pathogenesis of rheumatoid arthritis (RA). The interaction between NLCs established from RA patients (RA-NLCs), and freshly isolated blood monocytes was analyzed to further elucidate the pathogenesis of RA. RA-NLC lines were established from the synovium of RA patients. The RA-NLCs were cultured with monocytes freshly isolated from peripheral blood of healthy donors, and induction of interleukin (IL)-6 and IL-8 as well as the mRNA expression of these cytokines was examined. The levels of IL-6 were over 400 times higher in the supernatant from coculture of RA-NLCs and monocytes than in those from cultures of RA-NLCs alone. Anti-tumor necrosis factor (TNF)-alpha monoclonal antibody inhibited the induction of both cytokine in a dose-dependent fashion, although there was no detectable level of TNF-alpha in the supernatant from coculture. In addition, coculture of RA-NLCs and monocytes without direct cell contact did not induce cytokine production. To determine IL-6 producing cells, RA-NLCs and monocytes were separated into each fraction after coculture for 24 h. Cocultured RA-NLCs contained approximately 80 times higher IL-6 mRNA than the RA-NLCs cultured alone. The levels of IL-8 were also much higher (about 900 times) in the supernatant from coculture than in those from cultures of RA-NLCs alone. Cocultured RA-NLCs expressed IL-8 mRNA about 620 times higher than those cultured alone. These results indicate that NLCs produce high levels of IL-6 and IL-8 after cell-cell interaction with monocytes/macrophages via membrane-bound TNF-alpha, and that activation of NLCs by monocytes/macrophages may be involved in the pathogenesis of RA through maintenance of synovial inflammation.