Studies have demonstrated that production of IL-1Ra, a natural inhibitor of IL-1, is elevated in inflammatory RA joints [57]; however, the levels produced in RA joints are usually insufficient to reduce damage, as a concentration of 10-to-100-fold excess of IL-1Ra is required to effectively inhibit IL-1, which is a limiting factor for IL-1Ra as a clinical therapeutic [58]. Here, IL1A is linked to rheumatoid arthritis.