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Interleukin‐1β, Interleukin‐18, and the Interleukin‐1β Converting Enzyme a
Author(s) -
DINARELLO CHARLES A.
Publication year - 1998
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1998.tb08307.x
Subject(s) - interleukin 1β , interleukin , interleukin 15 , interleukin 11 , chemistry , medicine , cytokine , immunology
When injected intravenously into humans and animals, interleukin‐1β (IL‐1β) is perhaps the most potent of the endogenous pyrogens. However, IL‐1β is initially synthesized as a relatively inactive precursor molecule (proIL‐1β) which lacks a signal peptide and hence remains inside the cell. To be active as a fever‐producing molecule, proIL‐1β must first be processed to an active mature molecule and secreted. Although several enzymes associated with inflammatory tissues are capable of processing proIL‐1β into an active molecule in the extracellular compartment, the IL‐1β converting enzyme (ICE, also called caspase‐1) cuts intracellular proIL‐1β after the aspartic acid residue in position 116, resulting in a highly active mature IL‐1β 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‐1β, proIL‐18 is cleaved by ICE to yield an active molecule. However, unlike IL‐1β, 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‐γ production.