Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1988 Jul;85(14):5235–5239. doi: 10.1073/pnas.85.14.5235

Infusions of recombinant human interleukins 1 alpha and 1 beta cause hypercalcemia in normal mice.

M Sabatini 1, B Boyce 1, T Aufdemorte 1, L Bonewald 1, G R Mundy 1
PMCID: PMC281724  PMID: 3260671

Abstract

The immune cell products interleukins 1 alpha and -beta, which stimulate osteoclast activity in vitro, are among the most potent bone resorbing factors so far described. Although it appears likely that these cytokines are involved in regulation of trabecular bone turnover, nothing is known of their effects on extracellular fluid calcium concentration. In this report, we show the effects of 72-hr subcutaneous infusions of interleukins 1 alpha and -beta on plasma calcium and bone morphology in mice. Both interleukins 1 caused a marked dose-dependent increase in the plasma calcium. In higher doses, which cause the animals to die, the plasma calcium fell preterminally. Quantitative histomorphometry of bone sections showed evidence of increased numbers of osteoclasts and bone resorption surfaces. The effects were similar to those obtained with infusions of parathyroid hormone. These data suggest that in addition to its potential influence on trabecular bone volume, interleukin 1 may also modulate extracellular fluid calcium homeostasis under conditions in which it is produced excessively.

Full text

PDF
5235

Images in this article

Selected References

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

  1. Anast C. S., Forte L. F. Parathyroid function and magnesium depletion in the rat. Endocrinology. 1983 Jul;113(1):184–189. doi: 10.1210/endo-113-1-184. [DOI] [PubMed] [Google Scholar]
  2. Bertolini D. R., Nedwin G. E., Bringman T. S., Smith D. D., Mundy G. R. Stimulation of bone resorption and inhibition of bone formation in vitro by human tumour necrosis factors. Nature. 1986 Feb 6;319(6053):516–518. doi: 10.1038/319516a0. [DOI] [PubMed] [Google Scholar]
  3. Caverzasio J., Rizzoli R., Dayer J. M., Bonjour J. P. Interleukin-1 decreases renal sodium reabsorption: possible mechanism of endotoxin-induced natriuresis. Am J Physiol. 1987 May;252(5 Pt 2):F943–F946. doi: 10.1152/ajprenal.1987.252.5.F943. [DOI] [PubMed] [Google Scholar]
  4. Dewhirst F. E., Stashenko P. P., Mole J. E., Tsurumachi T. Purification and partial sequence of human osteoclast-activating factor: identity with interleukin 1 beta. J Immunol. 1985 Oct;135(4):2562–2568. [PubMed] [Google Scholar]
  5. Garrett I. R., Durie B. G., Nedwin G. E., Gillespie A., Bringman T., Sabatini M., Bertolini D. R., Mundy G. R. Production of lymphotoxin, a bone-resorbing cytokine, by cultured human myeloma cells. N Engl J Med. 1987 Aug 27;317(9):526–532. doi: 10.1056/NEJM198708273170902. [DOI] [PubMed] [Google Scholar]
  6. Gowen M., Mundy G. R. Actions of recombinant interleukin 1, interleukin 2, and interferon-gamma on bone resorption in vitro. J Immunol. 1986 Apr 1;136(7):2478–2482. [PubMed] [Google Scholar]
  7. Gowen M., Nedwin G. E., Mundy G. R. Preferential inhibition of cytokine-stimulated bone resorption by recombinant interferon gamma. J Bone Miner Res. 1986 Oct;1(5):469–474. doi: 10.1002/jbmr.5650010511. [DOI] [PubMed] [Google Scholar]
  8. Gowen M., Wood D. D., Ihrie E. J., McGuire M. K., Russell R. G. An interleukin 1 like factor stimulates bone resorption in vitro. Nature. 1983 Nov 24;306(5941):378–380. doi: 10.1038/306378a0. [DOI] [PubMed] [Google Scholar]
  9. Heath J. K., Saklatvala J., Meikle M. C., Atkinson S. J., Reynolds J. J. Pig interleukin 1 (catabolin) is a potent stimulator of bone resorption in vitro. Calcif Tissue Int. 1985 Jan;37(1):95–97. doi: 10.1007/BF02557686. [DOI] [PubMed] [Google Scholar]
  10. Horton J. E., Raisz L. G., Simmons H. A., Oppenheim J. J., Mergenhagen S. E. Bone resorbing activity in supernatant fluid from cultured human peripheral blood leukocytes. Science. 1972 Sep 1;177(4051):793–795. doi: 10.1126/science.177.4051.793. [DOI] [PubMed] [Google Scholar]
  11. Laemmli U. K., Favre M. Maturation of the head of bacteriophage T4. I. DNA packaging events. J Mol Biol. 1973 Nov 15;80(4):575–599. doi: 10.1016/0022-2836(73)90198-8. [DOI] [PubMed] [Google Scholar]
  12. Lomedico P. T., Kilian P. L., Gubler U., Stern A. S., Chizzonite R. Molecular biology of interleukin-1. Cold Spring Harb Symp Quant Biol. 1986;51(Pt 1):631–639. doi: 10.1101/sqb.1986.051.01.075. [DOI] [PubMed] [Google Scholar]
  13. Mundy G. R., Raisz L. G., Cooper R. A., Schechter G. P., Salmon S. E. Evidence for the secretion of an osteoclast stimulating factor in myeloma. N Engl J Med. 1974 Nov 14;291(20):1041–1046. doi: 10.1056/NEJM197411142912001. [DOI] [PubMed] [Google Scholar]
  14. Tsang V. C., Peralta J. M., Simons A. R. Enzyme-linked immunoelectrotransfer blot techniques (EITB) for studying the specificities of antigens and antibodies separated by gel electrophoresis. Methods Enzymol. 1983;92:377–391. doi: 10.1016/0076-6879(83)92032-3. [DOI] [PubMed] [Google Scholar]
  15. Weinberg J. B., Chapman H. A., Jr, Hibbs J. B., Jr Characterization of the effects of endotoxin on macrophage tumor cell killing. J Immunol. 1978 Jul;121(1):72–80. [PubMed] [Google Scholar]
  16. Wingfield P., Payton M., Tavernier J., Barnes M., Shaw A., Rose K., Simona M. G., Demczuk S., Williamson K., Dayer J. M. Purification and characterization of human interleukin-1 beta expressed in recombinant Escherichia coli. Eur J Biochem. 1986 Nov 3;160(3):491–497. doi: 10.1111/j.1432-1033.1986.tb10066.x. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES