Previously, it has been shown that in vitro, EV-ICs caused marked upregulation of leukotriene-B4 production by neutrophils10; however, several studies have shown that monocyte/macrophage are the major source of proinflammatory cytokines and chemokines in the inflamed RA joints, including TNF-α and IL-1β35. This evidence concerns the gene TNF and rheumatoid arthritis.