STIMULATION BY INTERLEUKIN-1 OF RENAL CALCIUM REABSORPTION IN THYROPARATHYROIDECTOMIZED RATS

Recombinant human interleukin-1 (rhIL-1) can induce an elevation in ca lcium that has been ascribed exclusively to the stimulation of bone re sorption. In the present study, we investigated whether rhIL-1 could a lso enhance the renal tubular reabsorption of calcium. The chronic inf luence of recombinant human rhIL-1 on renal calcium transport was inve stigated in thyroparathyroidectomized rats. Administration of rhIL-1 a t the dose of 1.5 mug/day sc for 6 days induced a significant elevatio n 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 pla sma calcium levels, as achieved by acutely infusing calcium gluconate, indicates that rhIL-1 enhanced the tubular reabsorption of calcium. T he 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 ren al handling of calcium was not associated with stimulation of the tubu lar reabsorption of magnesium. Acute administration of a large dose (2 4 mug given in a bolus IV injection) of rhIL-1 enhanced within minutes the urinary excretion of prostaglandin E2. This effect was followed b y a significant increase in urinary cAMP excretion and associated with a lower urinary calcium excretion. In conclusion, the results present ed in this study indicate that rhIL-1 administered chronically selecti vely stimulated the tubular reabsorption of calcium. Experimental evid ence suggests that this effect is mediated by prostaglandin-induced cA MP generation. These data strongly suggest that changes in the tubular handling of calcium could contribute to rhIL-1-induced hypercalcemia.