Interleukin-1 beta, interleukin-18, and the interleukin-1 beta converting enzyme

Ann N Y Acad Sci. 1998 Sep 29;856:1-11. doi: 10.1111/j.1749-6632.1998.tb08307.x.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Caspase 1 / physiology*
  • Fever / immunology
  • Fever / physiopathology*
  • Humans
  • Inflammation / immunology
  • Inflammation / physiopathology
  • Interleukin-1 / pharmacology
  • Interleukin-1 / physiology*
  • Interleukin-18 / pharmacology
  • Interleukin-18 / physiology*
  • Mice
  • Pyrogens*

Substances

  • Interleukin-1
  • Interleukin-18
  • Pyrogens
  • Caspase 1