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Interleukin-1β and Interleukin-18: Two Cytokine Precursors for Interleukin-1 β Converting Enzyme (Caspase-1)

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Book cover Immune Response in the Critically Ill

Part of the book series: Update in Intensive Care Medicine ((UICMSOFT,volume 31))

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Abstract

During the analysis of the human interleukin (IL)-1β precursor cDNA [1], the open reading frame resulted in a protein with a molecular weight of 31000 Daltons but lacking a signal peptide. The interpretation of this leaderless precursor of IL-1β was rather difficult since it was not clear how the mature form was cleaved naturally. We had expressed an intermediate form of recombinant IL-1β with a molecular weight of 21000 Daltons. This species of IL-1β was biologically weak. Upon cleavage with elastase, an 18000 IL-1β form resulted, which possessed a 100-fold increase in biological activity [2]. The elastase N-terminus was not that of the natural IL-1β reported in 1985 by the Belgians which had an N-terminus at alanine 117 [3]. That N-terminus indicated no specific cleavage protease and therefore, it remained unclear for several years exactly how and what protease cleaved precursor IL-1β into a mature peptide with an N-terminus at alanine 117. The discovery of the IL-1β converting enzyme (ICE) as a unique intracellular protease opened a door on an entirely new area of cytokine biology and inflammation in that there are intracellular proteases which function to cleave proteins which lack a classic signal peptide. ICE was the first enzyme of this class described for cutting the precursor for IL-1β; other members of the ICE family were clearly involved in other intracellular biological processes.

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Authors and Affiliations

  1. Department of Infectious Diseases, University Health Sciences Center, Denver, Colorado, USA

    C. A. Dinarello

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  1. C. A. Dinarello
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Editors and Affiliations

  1. Department of Surgery Interdepartmental Division of Critical Care Medicine, Toronto General Hospital University of Toronto, Toronto, Ontario, Canada

    John C. Marshall MD (Professor of Surgery) (Professor of Surgery)

  2. Department of Infectious Diseases & Microbiology Division of Investigative Science, Imperial College School of Medicine Hammersmith Hospital, London, UK

    Jonathan Cohen FRCP, FRCPath, FRCPE, FMedSci (Chairman) (Chairman)

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Dinarello, C.A. (2002). Interleukin-1β and Interleukin-18: Two Cytokine Precursors for Interleukin-1 β Converting Enzyme (Caspase-1). In: Marshall, J.C., Cohen, J. (eds) Immune Response in the Critically Ill. Update in Intensive Care Medicine, vol 31. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-57210-4_6

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  • DOI: https://doi.org/10.1007/978-3-642-57210-4_6

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-42589-2

  • Online ISBN: 978-3-642-57210-4

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