title: Parathyroid hormone induces hepatic production of bioactive interleukin-6 and its soluble receptor.
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 approximately 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.
authors.affiliation: Yale University School of Medicine, New Haven, CT 06520-8020, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Mitnick
authors.forename: A
authors.initials: A
authors.lastname: Grey
authors.forename: U
authors.initials: U
authors.lastname: Masiukiewicz
authors.forename: M
authors.initials: M
authors.lastname: Bartkiewicz
authors.forename: L
authors.initials: L
authors.lastname: Rios-Velez
authors.forename: S
authors.initials: S
authors.lastname: Friedman
authors.forename: L
authors.initials: L
authors.lastname: Xu
authors.forename: M C
authors.initials: MC
authors.lastname: Horowitz
authors.forename: K
authors.initials: K
authors.lastname: Insogna
mesh_terms: D000818:Animals; D002455:Cell Division; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D022781:Hepatocytes / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D007728:Kupffer Cells / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D019947:Receptors, Interleukin-6 / Q000096:biosynthesis*
chemical_list: D015850:Interleukin-6; D010281:Parathyroid Hormone; D010446:Peptide Fragments; D012333:RNA, Messenger; D019947:Receptors, Interleukin-6