IL-1 is one of a family of cytokines that include IL-1α, IL-1β, IL-18, IL-33, IL-35, IL-36, IL-37 and the anti-inflammatory cytokines IL-1Ra and IL-136Ra that play a vital role in inflammatory responses during infection and in autoimmune diseases. IL-1 was originally called endogenous pyrogen, through its ability to induce fever and was later assigned additional biological functions, including neutrophil recruitment and lymphocyte activation and is now recognized as major mediator of inflammation. Excessive IL-1β drives the recurrent episodes of fever and systemic inflammation in autoinflammatory diseases, such as gout, familial cold autoinflammatory syndrome and Muckle-Wells syndrome. IL-1β, together with tumor necrosis factor-α (TNF-α) and IL-6, also has a key role in the pathology of many autoimmune diseases, including rheumatoid arthritis and multiple sclerosis, caused by uncontrolled pathogenic T cell and antibody responses to self antigens.
IL-1β and IL-18 require cleavage by caspase-1 in the inflammasome to generate the mature active cytokines. IL-1β, IL-1α or IL-18 in combination with IL-23 can induce IL-17 production by γδ T cells without T cell receptor (TCR) engagement. IL-1β and IL-23 can also synergise to induce IL-17 production by iNKT cells and innate lymphoid cells (ILCs). Furthermore, CD4+αβ effector memory T cells secrete IL-17 in response to IL-23 in combination with either IL-1β or IL-18, in the absence of any TCR stimulation. The early IL-17 produced by innate cells induces recruitment of neutrophils to the site of infection, stimulates local epithelial cells to secrete anti-microbial proteins and promotes production of matrix metalloproteinases. Caspase-1 processed IL-1 family cytokines therefore play a vital role in the innate immune response and induction of IL-17 from innate immune cells which functions to fight infections and promote autoimmunity.
Disclosure of Interest K. Mills Shareholder of: Opsona Therapeutics and TriMod Therapeutics