Interleukin 1 (IL-1) refers to two proteins encoded by two different genes (IL-1a and IL-1b), both of which share the same cell surface receptors. IL-1a is a proinflammatory cytokine typically expressed under normal conditions in skin keratinocytes, some epithelial cells as well as some cells in the central nervous system. Under pathological conditions, IL-1a is also strongly expressed by monocytes, tissue macrophages, dendritic cells, B lymphocytes and NK cells. IL-1a is synthesized as a 31kDa precursor, some of which is cleaved prior to secretion into a 17.5kDa protein. IL-1a is biologically active both in a paracrine or systemic mode of action. The paracrine effects are mediated by the uncleaved portion of IL-1a, which is transported to the cell surface where it activates the IL-1 receptor type I (IL-1RI) of adjacent cells. The systemic effect is mediated by cleaved IL-1a, which is secreted into the bloodstream.

Signaling of IL-1 via its receptor, results in recruitment of the IL-1 R accessory protein (IL-1RAcP). This leads to a series of phosphorylation and ubiquitination events that ultimately activate the nuclear factor kB (NF-kB) and signal via the c-Jun N-terminal kinase (JNK) and the p38 mitogen-activated protein kinase (MAPK) pathways. These signaling events generate local and systemic responses that mediate acute phase inflammation, a critical host response to injury and infection. Under these circumstances, IL-1 induces fever, pain sensitivity, vasodilation, hypotention and slow wave sleep. All these responses are essential processes geared towards the re-establishment of tissue homeostasis. However, prolonged and inappropriate IL-1 induction has been shown to be associated with sepsis, rheumatoid arthritis, inflammatory bowel disease, acute and chronic myelogenous leukemia, insulin-dependent diabetes mellitus and atherosclerosis.