proIL1

proIL-1 refers to the inactive precursor forms of interleukin-1, mainly pro-IL-1β and pro-IL-1α. These precursors are produced from the IL1B and IL1A genes, respectively, and are expressed by a range of cells including monocytes, macrophages, dendritic cells, and epithelial cells in response to inflammatory stimuli such as pathogens or tissue damage.

Activation and processing are different for the two forms. Pro-IL-1β requires proteolytic processing by caspase-1 within inflammasomes to generate mature IL-1β, which is then secreted and capable of signaling. Pro-IL-1α can be active in its precursor form and may be cleaved by proteases such as calpain to yield a mature form; release commonly accompanies cell damage. Once activated, IL-1 peptides signal through the IL-1 receptor type I in conjunction with the IL-1 receptor accessory protein, triggering downstream signaling pathways.

Function and effects are central to the inflammatory response. IL-1 signaling activates transcription factors such as NF-κB and MAPKs, leading to the expression of inflammatory genes, fever induction, leukocyte recruitment, and acute phase responses. Regulation is tight: IL-1 receptor antagonist (IL-1Ra) and other decoy mechanisms limit signaling to prevent excessive inflammation.

Clinical relevance is notable. Dysregulation of pro-IL-1 production or maturation is implicated in autoinflammatory and autoimmune diseases, including CAPS, rheumatoid arthritis, gout, and inflammatory bowel disease. Therapeutic approaches target IL-1 signaling, with agents such as anakinra (IL-1 receptor antagonist), canakinumab (anti-IL-1β antibody), and rilonacept (IL-1 trap) used to treat these conditions.

In research, measuring pro-IL-1 precursors helps assess inflammasome activation and inflammatory state, complementing analyses of mature IL-1 activity.