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- _4 value "Besides its direct angiogenic role, other potential mechanisms of the angiogenic function of IL-18 may be through IL-8 and other angiogenic cytokines that it up-regulates. Indeed, IL-18 exerts an inflammatory cytokine cascade in the mixed PBMC population by stimulating the constitutive expression of IL-18R on NK cells and lymphocytes, which leads to TNF-a production, ultimately stimulating macrophage IL-1b and IL-8 production (19). In turn, treatment with IL-1b and TNF-a of RA synovial fibroblast cultures, not constitutively expressing IL-18, induced IL-18 gene and protein production, suggesting a feedback interaction to promote Th1 cytokine and cell development in RA (21)." provenance.