The role of IL-18 in bone destruction due to cancer metastasis

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1. The role of Interleukin (IL)-18 in bone resorption due to metastatic cancer :(1) Expression of IL-18 receptor in osteoblast and osteoclast : IL-18 receptor was detected in both osteoblast and osteoclast by immunohistochemical technique. The presence of mRNAs for IL-18 receptor components was also expressed by reverse transcriptase polymerase chain reaction in these cells.(2) The role of IL-18 in osteoclastic bone resporption in vitro condition : Osteoclastic bone resorption, purified from mice, was inhibited in co-culture with IL-18.(3) The role of IL-18 in osteoclastic bone resporption in vivo condition : The model of bone metastasis was established by an intracardiac injection of human breast cancer cells (MDA-231) and myeloma cell (ARH-77) in nude mice. IL-18 inhibited osteolytic growth of the cancer at bone metastatic sites.(4) The mechanism of the suppression of bone destruction by IL-18 : This activity could be synergistically enhanced by IL-12 followed by interferon gamma (IFN-γ) production.2. The role of IL-18 in pathogenesis of osteoarthritis (OA) and rheumatoid arthritis (RA).(1) The role of IL-18 in cartilage degradation of OA : There was a relatively strong correlation of IL-18 to prostaglandin (PG)E^2 in the synovial fluid of OA.IL-18 plays an important role in the pathogenesis of OA through the PGE^2 release.(2) Production of IL-18 in RA : IL-18 has been reported as a proinflammatory cytokine in rheumatoid arthritis (RA). We determined the IL-18 release in CD14+ macrophages by stimulation of soluble Fas ligand.In conclusion, targeting the IL-18 appears to be an important therapeutic approach to prevent bone destruction and articular cartilage degradation, in diseases such as metastatic bone tumor, OA, and RA.