IL-6 negatively regulates IL-11 production in vitro and in vivo

IL-6 and IL-11 are two cytokines that increase osteoclast formation and aug ment bone resorption. PTH stimulates the production of both cytokines by hu man osteoblast-like cells. Circulating levels of IL-6 are elevated in patie nts with states of PTH excess and correlate strongly to markers of bone res orption. In contrast, serum levels of IL-11 were significantly reduced in p atients with primary hyperparathyroidisin compared with values in euparathy roid controls. Further, after successful parathyroid adenomectomy, circulat ing levels of IL-6 fell, whereas IL-I I levels increased. Five-day infusion s of human PTH-(1-84) in rodents resulted in a significant decline in mean circulating levels of IL-11, whereas IL-6 levels significantly increased. P retreatment of cells and mice with neutralizing serum to IL-6 enhanced PTH- induced IL-11 production compared with the effect of pretreatment with noni mmune sera. These data indicate that IL-6 negatively regulates IL-11 produc tion in vivo and in vitro. Analysis of steady state mRNA levels in SaOS-2 c ells indicated that this effect is posttranscriptional. As both IL-6 and IL -11 stimulate osteoclast formation, down-regulation of IL-11 by IL-6 may he lp modulate the resorptive response to PTH.