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 augment bone resorption. PTH stimulates the production of both cytokines by human osteoblast-like cells. Circulating levels of IL-6 are elevated in patients with states of PTH excess and correlate strongly to markers of bone res...

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Bibliographic Details
Published in:Endocrinology (Philadelphia) 2001-09, Vol.142 (9), p.3850-3856
Main Authors: Nakchbandi, Inaam A, Mitnick, Mary Ann, Masiukiewicz, Urszula S, Sun, Ben hua, Insogna, Karl L
Format: Article
Language:English
Subjects:
Bone growth
Bone resorption
Circulation
Cytokines
Hyperparathyroidism
Interleukin 11
Interleukin 6
mRNA
Parathyroid hormone
Post-transcription
Pretreatment
Serum levels
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Summary:IL-6 and IL-11 are two cytokines that increase osteoclast formation and augment bone resorption. PTH stimulates the production of both cytokines by human osteoblast-like cells. Circulating levels of IL-6 are elevated in patients with states of PTH excess and correlate strongly to markers of bone resorption. In contrast, serum levels of IL-11 were significantly reduced in patients with primary hyperparathyroidism compared with values in euparathyroid controls. Further, after successful parathyroid adenomectomy, circulating levels of IL-6 fell, whereas IL-11 levels increased. Five-day infusions 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. Pretreatment of cells and mice with neutralizing serum to IL-6 enhanced PTH-induced IL-11 production compared with the effect of pretreatment with nonimmune sera. These data indicate that IL-6 negatively regulates IL-11 production in vivo and in vitro. Analysis of steady state mRNA levels in SaOS-2 cells 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 help modulate the resorptive response to PTH.
ISSN:0013-7227
1945-7170
DOI:10.1210/endo.142.9.8368