Evidence that interleukin-1 mediates its effects on bone resorption via the 80 kilodalton interleukin-1 receptor

I. Ross Garrett, Theresa A. Guise, Lynda F. Bonewald, Richard Chizzonite, Gregory R. Mundy

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Interleukin-1 (IL-1) mediates its effects through two distinct receptors, one of 80 kilodaltons (80 kD) present in athymic lymphocytes and fibroblasts, and one of 60 kD present in cells of the monocyte-macrophage lineage. A novel monocyte cytokine in the IL-1 family which binds to both the 80 and the 60 kD receptors has been purified, cloned, and expressed. As the interleukin-1 receptor antagonist (IL-1ra) has been shown to inhibit bone resorption in organ culture, it is not clear whether these effects are mediated through the 80 or the 60 kD receptor. Recently, neutralizing antibodies (35F5) have been developed to the 80 kD receptor which inhibit IL-1 effects mediated through this receptor. To determine the importance of the 80 kD receptor to IL-1-mediated bone resorption, we used the neutralizing antibodies (35F5) to the 80 kD receptor to determine if they inhibited bone resorption stimulated by IL-1 in bone organ cultures. The 35F5 antibody blocked bone-resorbing activity due to IL-1 completely, and also blocked control or "endogenous" bone-resorbing activity present in murine bone organ cultures incubated in control media. The 35F5 antibody had no effect on bone resorption mediated by tumor necrosis factor (TNF), or parathyroid hormone (PTH). These data suggest that the availability of the 80 kD IL-1 receptor is required for osteoclastic bone resorption mediated by IL-1.

Original languageEnglish (US)
Pages (from-to)438-441
Number of pages4
JournalCalcified Tissue International
Volume52
Issue number6
DOIs
StatePublished - Jun 1993
Externally publishedYes

Keywords

  • Bone resorption
  • Interleukin-1
  • Receptor antibodies

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine
  • Endocrinology

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