Interleukin-1 beta stimulates bone resorption and inhibits bone formation in vivo.
Interleukin-1 beta (IL-1 beta) and several other cytokines, including IL-1 alpha, tumor necrosis factor (TNF), and lymphotoxin, stimulate bone resorption and also inhibit bone formation in vitro. These effects are consistent with an uncoupling function for these mediators, although the effect of in vivo regulatory mechanism(s) that couple resorption and formation cannot be adequately evaluated in vitro. In the present studies, the effect of IL-1 beta on bone resorption and formation was determined in adult rats in vivo. Resorption was assessed by serum and urinary calcium levels, osteoclast number, and active resorption surface. Bone formation was determined by measurement of serum osteocalcin levels, and by quantitation of bone apposition rate using tetracycline labeling. A modest dose of IL-1 beta (1 microgram/kg) was found to stimulate transient increases in serum calcium, and a persistent elevation of urinary calcium excretion. IL-1 beta treatment also resulted in decreases in serum iron levels and in the albumin/globulin ratio, well-established in vivo effects of IL-1. SGOT, SGPT, BUN, creatinine, and total protein were unaffected, indicating that IL-1 beta treatment did not compromise kidney or liver function, and that animals were systemically healthy. This was further evidenced by normal weight gain in IL-1 beta-treated animals. Low doses (50 micrograms/kg) of synthetic human parathyroid hormone (PTH 1-34) also stimulated resorption, as shown by a sustained increase in serum calcium without increased urinary excretion. Both IL-1 beta and parathyroid hormone (PTH) stimulated similar increases in osteoclast number (N.Oc) and active resorption surface [Oc.S(%)].(ABSTRACT TRUNCATED AT 250 WORDS)
Nguyen
L
L
Department of Immunology, Forsyth Research Institute, Boston, MA.
Dewhirst
F E
FE
Hauschka
P V
PV
Stashenko
P
P
D000818:Animals; D001846:Bone Development / Q000187:drug effects*; D001862:Bone Resorption / Q000139:chemically induced*; D002118:Calcium / Q000097:blood; D005260:Female; D007375:Interleukin-1 / Q000494:pharmacology*; D015675:Osteocalcin / Q000097:blood; D010281:Parathyroid Hormone / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D019379:Teriparatide
D007375:Interleukin-1; D010281:Parathyroid Hormone; D010446:Peptide Fragments; D015675:Osteocalcin; D019379:Teriparatide; D002118:Calcium