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. Mouse IL-1a is a pro-inflammatory cytokine that encodes a 270 aa residue called pro-IL-1a, which contains a nuclear localization sequence, an N-myristoylation site, and three potential N-linked glycosylation sites. Primarily, pro-IL-1a is localized to the cytosol after synthesis. However, some pro-IL-1a is secreted and is subsequently cleaved by extracellular proteases such as calpain to form the 17 kDa, 154 aa residue mature IL-1a. Importantly, both pro-IL-1a and mature IL-1a have been shown to bind the IL-1 receptor and are biologically active. This is different than pro-IL-1b and mature IL-1b, where pro-IL-1b is biologically inactive. Within the mature protein, rat IL-1a and human IL-1a share 79% and 56% aa sequence identity, respectively, with the mouse IL-1a protein.

IL-1a and IL-1b interact with three type I transmembrane Ig superfamily proteins: IL-1 receptor type I (IL-1 RI), IL-1 RII, and IL-1 receptor accessory protein (IL-1 RAcP). Both IL-1 RI and IL-1 RII can bind directly to IL-1a and IL-1b. IL-1 RAcP interacts with IL-1 RI in the presence of IL-1 to form a high-affinity receptor complex that is required for intracellular signal transduction. Interestingly, IL-1 RAcP will also bind IL-1 RII, but this creates a non-functional high-affinity receptor complex that does not transduce IL-1 signals. Thus, IL-1 RII can act to moderate the function of IL-1a and IL-1b.

IL-1a is typically expressed under normal conditions in skin keratinocytes and some epithelial cells, as well as in 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. Intracellular pro-IL-1a can also be localized to the nucleus where it plays a role as an intracellular regulator of human endothelial cell proliferation and migration. IL-1 possesses a wide variety of biological activities and plays a central role in mediating immune and inflammatory responses. Normal production of IL-1 is critical for hematopoiesis, osteoclast differentiation, and initiation of normal host responses to stresses such as injury and infection. Incorrect production of IL-1 has been shown to be associated with a variety of pathological conditions including sepsis, rheumatoid arthritis, inflammatory bowel disease, acute and chronic myelogenous leukemia, insulin-dependent diabetes mellitus, and atherosclerosis.