Parathyroid hormone induces hepatic production of bioactive interleukin-6 and its soluble receptor

Mary Ann Mitnick, Andrew Grey, Urszula Masiukiewicz, Marcjanna Bartkiewicz, Laura Rios-Velez, Scott Friedman, Lieming Xu, Mark C. Horowitz, Karl Insogna

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73 Scopus citations

Abstract

Interleukin-6 (IL-6) is an important mediator of parathyroid hormone (PTH)-induced bone resorption. Serum levels of IL-6 and its soluble receptor (IL-6sR) are regulated in part by PTH. The PTH/PTH-related protein type 1 receptor is highly expressed in the liver, and in the current study we investigated whether the liver produces IL-6 or IL-6sR in response to PTH. Perfusion of the isolated rat liver with PTH-(1-84) stimulated rapid, dose-dependent production of bioactive IL-6 and the IL-6sR. These effects were observed at near physiological concentrations of the hormone such that 1 pM PTH induced hepatic IL-6 production at a rate of ∼0.6 ng/min. In vitro, hepatocytes, hepatic endothelial cells, and Kupffer cells, but not hepatic stellate cells, were each found to produce both IL-6 and IL-6sR in response to higher (10 nM) concentrations of PTH. Our data suggest that hepatic-derived IL-6 and IL-6sR contribute to the increase in circulating levels of these cytokines induced by PTH in vivo and raise the possibility that PTH-induced, liver-derived IL-6 may exert endocrine effects on tissues such as bone.

Original languageEnglish
Pages (from-to)E405-E412
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume280
Issue number3 43-3
DOIs
StatePublished - Mar 2001

Keywords

  • Bone
  • Cytokines
  • Hepatic endothelial cells
  • Hepatocytes
  • Kupffer cells

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