INTERLEUKIN-6 DOES NOT MEDIATE THE STIMULATION BY PROSTAGLANDIN-E(2),PARATHYROID-HORMONE, OR 1,25-DIHYDROXYVITAMIN-D-3 OF OSTEOCLAST DIFFERENTIATION AND BONE-RESORPTION IN NEONATAL MOUSE PARIETAL BONES

The cytokine interleukin-6 (IL-6) was produced by neonatal mouse parie tal bones during a 6- or 48-hour culture period in response to prostag landin E, (PGE,) and bovine parathyroid hormone (PTH) 1-34 fragment bu t not 1,25-dihydroxyvitamin D-3 [1,25(OH)(2)D-3]. At the same time the re was an increase in tartrate-resistant, acid phosphatase-positive os teoclasts (TRAP+OC) with all three osteotropic effecters over 6 hours, and an increase in Ca-45 release over 48 hours. TRAP+OC numbers on PG E(2)-stimulated bones were positively correlated with IL-6 concentrati on. Our aim was to determine if IL-6 mediated this response. Recombina nt human IL-6 (rhIL-6) was added to parietal bones in culture at conce ntrations within the range that PGE, or PTH would produce during incub ation. However, over 6 or 48 hours, rhIL-6 did not stimulate TRAP+OC t o increase in number nor did it cause an increase in calcium release o ver 48 hours. Adding an antibody against mouse IL-6 to bone cultures s timulated with PTH or PGE, neutralized the resulting IL-6 bioactivity by up to 92% but did not inhibit TRAP+OC formation. We conclude that a lthough IL-6 is produced in response to two important stimulators of b one resorption, it does not mediate osteoclast differentiation or bone resorption in this model.