The second arm of “IL-1 system” has been enlighted in 2009 with the identification (51) of the cause of a human autoinflammatory syndrome of skin and bone in a homozygous truncating mutations in the IL-1RN gene that leads to the lack of secretion of this receptor antagonist (IL-1RA), and as a consequence in an unopposed IL-1 signaling. The gene discussed is IL1A; the disease is autoinflammatory syndrome.