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

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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‐1α and β, 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.
Funding Information
  • National Institutes of Health (AR28149, CA-40035, DE08569)