Biological properties of recombinant human monocyte-derived interleukin 1 receptor antagonist

J Clin Invest. 1990 May;85(5):1694-7. doi: 10.1172/JCI114622.


Human monocytes cultured on adherent IgG produce a specific IL-1 inhibitor that functions as a receptor antagonist (IL-1ra). This molecular has been purified, sequenced, cloned as a cDNA, and expressed in Escherichia coli. Recombinant IL-1ra has 17,000 mol wt and binds to IL-1 receptors on T lymphocytes, synovial cells, and chondrocytes with an affinity nearly equal to that of IL-1. These studies have examined some biological properties of purified recombinant human IL-1ra. This protein exhibits a dose-responsive inhibition of Il-1 alpha and Il-1 beta augmentation of PHA-induced murine thymocyte proliferation. The recombinant IL-1ra also blocks IL-1 alpha and IL-1 beta stimulation of PGE2 production in human synovial cells and rabbit articular chondrocytes, and of collagenase production by the synovial cells. A 50% inhibition of these IL-1-induced biological responses requires amounts of IL-1ra up to 100-fold in excess of the amounts of IL-1 alpha or IL-1 beta present. IL-1ra may play an important role in normal physiology or in pathophysiological states by functioning as a natural IL-1 receptor antagonist in the cell microenvironment.

Publication types

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

MeSH terms

  • Animals
  • Cartilage, Articular / drug effects
  • Cartilage, Articular / metabolism
  • Cells, Cultured
  • Dinoprostone / biosynthesis
  • Escherichia coli / genetics
  • Humans
  • Interleukin-1 / pharmacology
  • Kinetics
  • Lymphocyte Activation / drug effects*
  • Mice
  • Mice, Inbred C3H
  • Monocytes / immunology*
  • Rabbits
  • Receptors, Immunologic / drug effects*
  • Receptors, Interleukin-1
  • Recombinant Proteins / isolation & purification
  • Recombinant Proteins / pharmacology
  • Synovial Membrane / drug effects
  • Synovial Membrane / metabolism
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*
  • Thymus Gland / immunology


  • Interleukin-1
  • Receptors, Immunologic
  • Receptors, Interleukin-1
  • Recombinant Proteins
  • Dinoprostone