Stimulation by interleukin-1 of renal calcium reabsorption in thyroparathyroidectomized rats.
Recombinant human interleukin-1 (rhIL-1) can induce an elevation in calcium that has been ascribed exclusively to the stimulation of bone resorption. In the present study, we investigated whether rhIL-1 could also enhance the renal tubular reabsorption of calcium. The chronic influence of recombinant human rhIL-1 on renal calcium transport was investigated in thyroparathyroidectomized rats. Administration of rhIL-1 at the dose of 1.5 micrograms/day sc for 6 days induced a significant elevation in plasma calcium that was associated with a slight but significant decrease in the urinary excretion of calcium. Recording of the urinary calcium excretion expressed per ml glomerular filtrate at various plasma calcium levels, as achieved by acutely infusing calcium gluconate, indicates that rhIL-1 enhanced the tubular reabsorption of calcium. The calculated index of the tubular reabsorption of calcium (TRCal) was significantly increased by rhIL-1 (2.18 +/- 0.14 versus 1.79 +/- 0.07 mmol/l GFR, p < 0.05, in vehicle-treated rats). The change in the renal handling of calcium was not associated with stimulation of the tubular reabsorption of magnesium. Acute administration of a large dose (24 micrograms given in a bolus IV injection) of rhIL-1 enhanced within minutes the urinary excretion of prostaglandin E2. This effect was followed by a significant increase in urinary cAMP excretion and associated with a lower urinary calcium excretion. In conclusion, the results presented in this study indicate that rhIL-1 administered chronically selectively stimulated the tubular reabsorption of calcium. Experimental evidence suggests that this effect is mediated by prostaglandin-induced cAMP generation. These data strongly suggest that changes in the tubular handling of calcium could contribute to rhIL-1-induced hypercalcemia.
Caverzasio
J
J
Department of Medicine, University Hospital of Geneva, Switzerland.
Rizzoli
R
R
Vallotton
M B
MB
Dayer
J M
JM
Bonjour
J P
JP
D000042:Absorption; D000818:Animals; D002118:Calcium / Q000097:blood / Q000378:metabolism* / Q000652:urine; D000242:Cyclic AMP / Q000652:urine; D015232:Dinoprostone / Q000096:biosynthesis / Q000652:urine; D007279:Injections, Subcutaneous; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology*; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism*; D008274:Magnesium / Q000097:blood / Q000652:urine; D008297:Male; D016105:Parathyroidectomy; D010710:Phosphates / Q000097:blood / Q000652:urine; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D013965:Thyroidectomy
D007375:Interleukin-1; D010710:Phosphates; D011994:Recombinant Proteins; D000242:Cyclic AMP; D008274:Magnesium; D015232:Dinoprostone; D002118:Calcium