Interleukin-1 receptor antagonist inhibits the hypercalcemia mediated by interleukin-1.
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.
University of Texas Health Science Center, San Antonio.
T A
TA
Guise
I R
IR
Garrett
L F
LF
Bonewald
G R
GR
Mundy
D000818:Animals; D001862:Bone Resorption / Q000517:prevention & control; D002118:Calcium / Q000097:blood*; D005260:Female; D006934:Hypercalcemia / Q000139:chemically induced / Q000517:prevention & control*; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000633:toxicity*; D051379:Mice; D008813:Mice, Inbred ICR; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects*; D010281:Parathyroid Hormone / Q000633:toxicity; D044162:Parathyroid Hormone-Related Protein; D011247:Pregnancy; D011506:Proteins / Q000633:toxicity; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011994:Recombinant Proteins / Q000633:toxicity; D012795:Sialoglycoproteins / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000633:toxicity
C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha; D002118:Calcium