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

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.