Long-term systemic administration of human recombinant interleukin-1beta induces a dose-dependent fall in circulating parathyroid hormone in rats.
The synergism/antagonism between interleukin (IL)-1beta and parathyroid hormone (PTH) has been the subject of in vitro and in vivo work, but a possible direct action of the cytokine on PTH release has not been reported. We have investigated the effect of a continuous infusion of human recombinant IL-1beta (rIL-1beta) on circulating PTH during a 14-day period in 7-week-old female rats. This time interval was chosen in order to exclude initial hypercalcemia and to enable data collection under steady-state conditions. Five groups of 20 animals each had miniosmotic pumps (Alzet 2002, 200 microl) implanted subcutaneously and primed to release either distilled water (controls) or 100, 500, 1,000 and 2, 000 ng/24 h of rIL-1beta. Blood was drawn on days 1 and 14 for PTH, corticosterone and Ca2+ determinations. Adequate biological activity of the infused rIL-1beta was supported by elevated rectal temperature records and significant elevations of plasma corticosterone on day 14. The 100-ng dose had no effect but 500-2, 000 ng rIL-1beta/24 h significantly reduced plasma PTH in a dose-dependent manner down to 54% of basal value (20.4 +/- 1.1 vs. 15.3 +/- 1.4 pg/ml for 500 ng, p < 0.005; 20.5 +/- 1.3 vs 12.3 +/- 1.1 for 1,000 ng, p < 0.001, and 19.5 +/- 2.0 vs. 10.6 +/- 1.1 pg/ml for 2,000 ng, p < 0.0008). Despite these findings, no differences in blood Ca2+ could be detected between treated animals and controls. The following conclusions can be inferred from the foregoing: Systemic administration of rIL-1beta to rats induced a dose-dependent fall in circulating PTH without altering calcemia, calling into question the biological relevance of the former finding. Although the recorded PTH depression may indeed not have been severe enough to cause hypocalcemia, it can be hypothesized that osteoclast activation by rIL-1beta would enhance bone mineral release into the pool compensating for depressed PTH activity.
Lippuner
K
K
Policlinic of Medicine, University Hospital of Bern, Bern, Switzerland.
del Pozo
E
E
MacKenzie
A
A
Jaeger
P
P
D000818:Animals; D002118:Calcium / Q000097:blood; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D010281:Parathyroid Hormone / Q000097:blood*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology
D007375:Interleukin-1; D010281:Parathyroid Hormone; D011994:Recombinant Proteins; D002118:Calcium