Interleukin‐1β, Interleukin‐18, and the Interleukin‐1β Converting Enzymea

Abstract

When injected intravenously into humans and animals, interleukin-1 beta (IL-1 beta) is perhaps the most potent of the endogenous pyrogens. However, IL-1 beta is initially synthesized as a relatively inactive precursor molecule (proIL-1 beta) which lacks a signal peptide and hence remains inside the cell. To be active as a fever-producing molecule, proIL-1 beta must first be processed to an active mature molecule and secreted. Although several enzymes associated with inflammatory tissues are capable of processing proIL-1 beta into an active molecule in the extracellular compartment, the IL-1 beta converting enzyme (ICE, also called caspase-1) cuts intracellular proIL-1 beta after the aspartic acid residue in position 116, resulting in a highly active mature IL-1 beta that is secreted into the extracellular space. IL-18 is also initially synthesized as an inactive precursor molecule (proIL-18) lacking a signal peptide. IL-18 is a member of the IL-1 family, and like IL-1 beta, proIL-18 is cleaved by ICE to yield an active molecule. However, unlike IL-1 beta, IL-18 is not an endogenous pyrogen following intraperitoneal injection into mice. Nevertheless, IL-18 may contribute to inflammation and fever because IL-18 is a potent inducer of tumor necrosis factor, chemokines, and interferon-gamma production.