IL-18 induces apoptosis of adherent bone marrow cells in TNF-α mediated osteoclast formation in synergy with IL-12

It has recently been reported that TNF-α has the ability to accelerate osteoclastogenesis. We previously reported that the proinflammatory cytokine IL-12 induced apoptosis in TNF-α-mediated osteoclastogenesis in mouse bone marrow culture through an interaction of Fas and Fas ligand (FasL). In this study, the effect of IL-18 was investigated, which is also a proinflammatory cytokine, on TNF-α-mediated osteoclastogenesis. When mouse bone marrow cells were cultured with both TNF-α and IL-18, the number of adherent cells in the culture decreased. Apoptotic effects, indicated by nuclear, cellular and DNA fragmentation, were observed in the adherent cells. The apoptosis was inhibited by an anti-FasL antibody. Apoptosis of the adherent bone marrow cells might be caused by Fas–FasL interactions. Furthermore, IL-18 and IL-12 synergistically induced apoptosis of adherent bone marrow cells in the presence of TNF-α, and up-regulated FasL transcription in non-adherent cells. The results suggested that FasL synergistically up-regulated by IL-12 and IL-18 increased apoptosis of the adherent cells.