Pro-inflammatory cytokines such as interleukin-1beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) released from the inflamed and damaged tissue of the local inflammatory response, and subsequent secretions including histamine, serotonin, bradykinin, ATP, prostaglandin E2 (PGE2) and protons (H+) play a predominant role in RA. This evidence concerns the gene IL1B and rheumatoid arthritis.