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 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.
Nakchbandi
I A
IA
Department of Medicine, Yale University School of Medicine, New Haven, Connecticut 06520-8020, USA.
Mitnick
M A
MA
Masiukiewicz
U S
US
Sun
B H
BH
Insogna
K L
KL
D000818:Animals; D002460:Cell Line; D005260:Female; D006801:Humans; D006961:Hyperparathyroidism / Q000097:blood; D066298:In Vitro Techniques; D017370:Interleukin-11 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000097:blood; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout / Q000235:genetics; D010006:Osteoblasts / Q000378:metabolism; D010281:Parathyroid Hormone / Q000494:pharmacology; D016105:Parathyroidectomy; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000093242:Interleukin-6 Inhibitors
D017370:Interleukin-11; D015850:Interleukin-6; D010281:Parathyroid Hormone; D012333:RNA, Messenger; D000093242:Interleukin-6 Inhibitors