Library Subscription: Guest
Begell Digital Portal Begell Digital Library eBooks Journals References & Proceedings Research Collections
Critical Reviews™ in Immunology
IF: 1.404 5-Year IF: 3.347 SJR: 0.706 SNIP: 0.55 CiteScore™: 2.19

ISSN Print: 1040-8401
ISSN Online: 2162-6472

Volume 40, 2020 Volume 39, 2019 Volume 38, 2018 Volume 37, 2017 Volume 36, 2016 Volume 35, 2015 Volume 34, 2014 Volume 33, 2013 Volume 32, 2012 Volume 31, 2011 Volume 30, 2010 Volume 29, 2009 Volume 28, 2008 Volume 27, 2007 Volume 26, 2006 Volume 25, 2005 Volume 24, 2004 Volume 23, 2003 Volume 22, 2002 Volume 21, 2001 Volume 20, 2000 Volume 19, 1999 Volume 18, 1998 Volume 17, 1997 Volume 16, 1996 Volume 15, 1995 Volume 14, 1994

Critical Reviews™ in Immunology

DOI: 10.1615/CritRevImmunol.v15.i1.30
pages 77-105

lnterleukin-1 Receptor Antagonist

Andrew C. Lennard
Yamanouchi Research Institute U.K., Littlemore Hospital, Oxford OX4 4XN, U.K.


The interleukin-1 receptor antagonist (IL-lra) is unusual in that it is the only known naturally occurring, cytokine receptor antagonist with no apparent agonist function. Over the last 5 years, since the cloning of the IL-lra cDNA sequence, there has been intensive research on the genetics, regulation, and potential therapeutic value of this protein. The later discovery of a second form of IL-lra in 1991 has complicated the picture. Whereas the originally described IL-lra is predominantly glycosylated and secreted (sIL-lra), the alternative isoform is unglycosylated and intracellular (icIL-lra). Although the biological roles of the two forms are still open to question, IL-lra is likely to be of great importance in the pathogenesis of both acute and chronic inflammatory diseases. A large body of evidence for this conclusion has come from animal models of inflammatory disease that respond well to administration of exogenous IL-lra. A role for recombinant IL-lra in the management of human disease is still under investigation. The two forms of IL-lra are encoded by a single gene by alternative usage of two first exons. Expression of sIL-lra and icIl-lra is regulated by two promoters. In this review I explore the genetics of the gene encoding IL-lra (IL-1RN) and the mechanisms of IL-lra gene activation to produce sIL-lra and icIL-lra. Also, possible biological roles for these immunomodulators in health and disease are discussed.

Articles with similar content:

lnterleukin-1 Receptor Antagonist
Critical Reviews™ in Immunology, Vol.37, 2017, issue 2-6
Andrew C. Lennard
Is the CD200/CD200 Receptor Interaction More Than Just a Myeloid Cell Inhibitory Signal?
Critical Reviews™ in Immunology, Vol.26, 2006, issue 3
Janet Liversidge, Konstantinos Minas
M1 and M2 Macrophages: Oracles of Health and Disease
Critical Reviews™ in Immunology, Vol.32, 2012, issue 6
Charles Mills
Function of Histone Deacetylase Inhibitors in Inflammation
Critical Reviews™ in Immunology, Vol.31, 2011, issue 3
Paul P. Tak, Kris A. Reedquist, Aleksander M. Grabiec
Therapeutic Targeting of the Epidermal Growth Factor Receptor in Human Cancer
Critical Reviews™ in Oncogenesis, Vol.17, 2012, issue 1
Nathalie S. Dhomen, Niall Tebbutt, John Mariadason, Andrew M. Scott