PROSTAGLANDIN E(2) STIMULATES THE PRODUCTION OF INTERLEUKIN-6 BY NEONATAL MOUSE PARIETAL BONES

The pleiotropic cytokine interleukin-6 (IL-6) is thought to be involve d in bone homeostasis. A number of bone resorbing agents have been sho wn to induce the release of IL-6 from bone. We wished to determine whe ther prostaglandin E(2) (PGE(2)), which is a mediator of bone resorpti on, can elicit the production of IL-6. IL-6 was measured by the prolif erative response of B9 hybridoma cells and could be completely neutral ised by an anti-IL-6 antibody. Parietal bones from neonatal mice were maintained in culture in the presence of indomethacin (10(-6) M) with or without PGE(2). The time course and dose-response to PGE(2) of IL-6 production were determined. After 6 h in culture, 10(-8) M PGE(2) pro duced significantly more IL-6 than the controls (P < 0.005). PGE(2) (1 0(-6) M) stimulated the production of a mean of 12.8 ng/ml IL-6 over 6 h. Preincubating bones with indomethacin for 20 h prior to a 6 h cult ure with indomethacin led to a lowering of the production of IL-6 (mea n 1.8 ng/ml) compared to bones cultured without the preincubation peri od (5.8 ng/ml). When the indomethacin preincubation period was used, a significant increase in IL-6 production was found with 10(-9) M PGE(2 ) (P < 0.005), and 10(-6) M PGE(2) caused the production of 39.9 ng/ml IL-6 over 6 h. Stripping endocranial and ectocranial membranes from b ones demonstrated the membranes to be the major site of IL-6 productio n. However, intact bones were required for maximal stimulated IL-6 pro duction.