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Interleukin-1 receptor antagonist inhibits the hypercalcemia mediated by interleukin-1.

Authors
  • Guise, T A
  • Garrett, I R
  • Bonewald, L F
  • Mundy, G R
Type
Published Article
Journal
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
Publication Date
May 01, 1993
Volume
8
Issue
5
Pages
583–587
Identifiers
PMID: 8511985
Source
Medline
License
Unknown

Abstract

Recently, the effects of interleukin-1 (IL-1) on bone resorption in organ culture have been shown to be inhibited by an interleukin-1 receptor antagonist (IL-1RA), a novel monocyte cytokine in the IL-1 family. IL-1RA, which binds to IL-1 receptors and inhibits many of the effects of IL-1 alpha and beta, has been purified, cloned, and expressed. We used IL-1RA to investigate its effects on calcium homeostasis in vivo. After confirming that IL-1RA completely inhibited the effects of IL-1 on bone resorption in organ cultures, we tested the effects of IL-1RA on hypercalcemia mediated by IL-1 in normal mice and found that prolonged hypercalcemia provoked by IL-1 was completely inhibited by IL-1RA. The initial transient decrease in blood ionized calcium observed following an injection of IL-1 was also abrogated. IL-1RA had no effect alone on blood ionized calcium or on hypercalcemia mediated by parathyroid hormone (PTH) or PTH-related protein (PTHrP). These data suggest that antagonists to the IL-1 receptor may provide a useful therapeutic approach to osteoclastic bone resorption and hypercalcemia that is IL-1 dependent.

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