IL-1β has no direct effect on mediating angiogenesis in RA, instead it indirectly mediates the pathophysiological angiogenesis via several of its downstream effectors upregulating the proangiogenic mediators angiopoietin-1 (ang-1), Tie-2, and VEGF in a JNK and p38 MAPK dependent pathway (55). This evidence concerns the gene IL1B and rheumatoid arthritis.