Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1990 May;85(5):1694–1697. doi: 10.1172/JCI114622

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

W P Arend 1, H G Welgus 1, R C Thompson 1, S P Eisenberg 1
PMCID: PMC296623  PMID: 2139669

Abstract

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.

Full text

PDF
1694

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arend W. P., Dayer J. M. Cytokines and cytokine inhibitors or antagonists in rheumatoid arthritis. Arthritis Rheum. 1990 Mar;33(3):305–315. doi: 10.1002/art.1780330302. [DOI] [PubMed] [Google Scholar]
  2. Arend W. P., Joslin F. G., Massoni R. J. Characteristics of chondrocyte responses to a human interleukin 1-like factor. Clin Immunol Immunopathol. 1985 Sep;36(3):358–370. doi: 10.1016/0090-1229(85)90056-x. [DOI] [PubMed] [Google Scholar]
  3. Arend W. P., Joslin F. G., Massoni R. J. Effects of immune complexes on production by human monocytes of interleukin 1 or an interleukin 1 inhibitor. J Immunol. 1985 Jun;134(6):3868–3875. [PubMed] [Google Scholar]
  4. Arend W. P., Joslin F. G., Thompson R. C., Hannum C. H. An IL-1 inhibitor from human monocytes. Production and characterization of biologic properties. J Immunol. 1989 Sep 15;143(6):1851–1858. [PubMed] [Google Scholar]
  5. Balavoine J. F., de Rochemonteix B., Williamson K., Seckinger P., Cruchaud A., Dayer J. M. Prostaglandin E2 and collagenase production by fibroblasts and synovial cells is regulated by urine-derived human interleukin 1 and inhibitor(s). J Clin Invest. 1986 Oct;78(4):1120–1124. doi: 10.1172/JCI112669. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bendtzen K., Mandrup-Poulsen T., Nerup J., Nielsen J. H., Dinarello C. A., Svenson M. Cytotoxicity of human pI 7 interleukin-1 for pancreatic islets of Langerhans. Science. 1986 Jun 20;232(4757):1545–1547. doi: 10.1126/science.3086977. [DOI] [PubMed] [Google Scholar]
  7. Bomsztyk K., Sims J. E., Stanton T. H., Slack J., McMahan C. J., Valentine M. A., Dower S. K. Evidence for different interleukin 1 receptors in murine B- and T-cell lines. Proc Natl Acad Sci U S A. 1989 Oct;86(20):8034–8038. doi: 10.1073/pnas.86.20.8034. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Chizzonite R., Truitt T., Kilian P. L., Stern A. S., Nunes P., Parker K. P., Kaffka K. L., Chua A. O., Lugg D. K., Gubler U. Two high-affinity interleukin 1 receptors represent separate gene products. Proc Natl Acad Sci U S A. 1989 Oct;86(20):8029–8033. doi: 10.1073/pnas.86.20.8029. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Cooper T. W., Bauer E. A., Eisen A. Z. Enzyme-linked immunosorbent assay for human skin collagenase. Coll Relat Res. 1983 May;3(3):205–215. doi: 10.1016/s0174-173x(83)80004-1. [DOI] [PubMed] [Google Scholar]
  10. Dayer J. M., Krane S. M., Russell R. G., Robinson D. R. Production of collagenase and prostaglandins by isolated adherent rheumatoid synovial cells. Proc Natl Acad Sci U S A. 1976 Mar;73(3):945–949. doi: 10.1073/pnas.73.3.945. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Dinarello C. A. Interleukin-1 and its biologically related cytokines. Adv Immunol. 1989;44:153–205. doi: 10.1016/s0065-2776(08)60642-2. [DOI] [PubMed] [Google Scholar]
  12. Eisenberg S. P., Evans R. J., Arend W. P., Verderber E., Brewer M. T., Hannum C. H., Thompson R. C. Primary structure and functional expression from complementary DNA of a human interleukin-1 receptor antagonist. Nature. 1990 Jan 25;343(6256):341–346. doi: 10.1038/343341a0. [DOI] [PubMed] [Google Scholar]
  13. Hannum C. H., Wilcox C. J., Arend W. P., Joslin F. G., Dripps D. J., Heimdal P. L., Armes L. G., Sommer A., Eisenberg S. P., Thompson R. C. Interleukin-1 receptor antagonist activity of a human interleukin-1 inhibitor. Nature. 1990 Jan 25;343(6256):336–340. doi: 10.1038/343336a0. [DOI] [PubMed] [Google Scholar]
  14. Larrick J. W. Native interleukin 1 inhibitors. Immunol Today. 1989 Feb;10(2):61–66. doi: 10.1016/0167-5699(89)90308-3. [DOI] [PubMed] [Google Scholar]
  15. Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983 Dec 16;65(1-2):55–63. doi: 10.1016/0022-1759(83)90303-4. [DOI] [PubMed] [Google Scholar]
  16. Muchmore A. V., Decker J. M. Uromodulin. An immunosuppressive 85-kilodalton glycoprotein isolated from human pregnancy urine is a high affinity ligand for recombinant interleukin 1 alpha. J Biol Chem. 1986 Oct 15;261(29):13404–13407. [PubMed] [Google Scholar]
  17. Rosenstreich D. L., Tu J. H., Kinkade P. R., Maurer-Fogy I., Kahn J., Barton R. W., Farina P. R. A human urine-derived interleukin 1 inhibitor. Homology with deoxyribonuclease I. J Exp Med. 1988 Nov 1;168(5):1767–1779. doi: 10.1084/jem.168.5.1767. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Roux-Lombard P., Modoux C., Dayer J. M. Production of interleukin-1 (IL-1) and a specific IL-1 inhibitor during human monocyte-macrophage differentiation: influence of GM-CSF. Cytokine. 1989 Nov;1(1):45–51. doi: 10.1016/1043-4666(89)91047-8. [DOI] [PubMed] [Google Scholar]
  19. Seckinger P., Lowenthal J. W., Williamson K., Dayer J. M., MacDonald H. R. A urine inhibitor of interleukin 1 activity that blocks ligand binding. J Immunol. 1987 Sep 1;139(5):1546–1549. [PubMed] [Google Scholar]
  20. Seckinger P., Williamson K., Balavoine J. F., Mach B., Mazzei G., Shaw A., Dayer J. M. A urine inhibitor of interleukin 1 activity affects both interleukin 1 alpha and 1 beta but not tumor necrosis factor alpha. J Immunol. 1987 Sep 1;139(5):1541–1545. [PubMed] [Google Scholar]
  21. Welgus H. G., Stricklin G. P. Human skin fibroblast collagenase inhibitor. Comparative studies in human connective tissues, serum, and amniotic fluid. J Biol Chem. 1983 Oct 25;258(20):12259–12264. [PubMed] [Google Scholar]
  22. Westcott J. Y., Chang S., Balazy M., Stene D. O., Pradelles P., Maclouf J., Voelkel N. F., Murphy R. C. Analysis of 6-keto PGF1 alpha, 5-HETE, and LTC4 in rat lung: comparison of GM/MS, RIA, and EIA. Prostaglandins. 1986 Dec;32(6):857–873. doi: 10.1016/0090-6980(86)90095-x. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES