IL-18, produced by macrophages, can cooperate with IL-12 to induce the expression of TNF-α, promote the occurrence of arthritis and the proliferation of synovial tissue. IL-18 stimulates the expression of iNOS, COX-2, IL-6 and other genes in articular chondrocytes, and induces the production of a large number of NO and PGE2, which participate in joint inflammation, injury and degeneration. IL-18 can induce chondrocytes to produce MMP-1, MMP-3, MMP-13 and promote the degradation of cartilage tissue. In addition, studies have confirmed that IL-18 up-regulates the expression of TNF receptor, VCAM-1 and ICAM-1 through NF-κB and PI3K pathways, thereby promoting the production of TNF-α by mononuclear cells/macrophages.