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Author Notes:

Correspondence: Dr Susan A. Safley, Department of Surgery, 5207 Woodruff Memorial Building, 1639 Pierce Drive, Atlanta, Georgia, USA 30322. E-mail: ssafley@emory.edu

Subjects:

Research Funding:

This research was made possible by a generous gift supporting the Elizabeth Brooke Gottlich Laboratory.

Keywords:

  • cytokines
  • hyperparathyroidism
  • interleukin-6
  • parathyroid
  • parathyroid hormone

Interleukin-6 production and secretion by human parathyroids

Tools:

Journal Title:

Clinical and Experimental Immunology

Volume:

Volume 136, Number 1

Publisher:

, Pages 145-156

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Parathyroid hormone (PTH) stimulates osteoblasts to produce the proinflammatory cytokine interleukin-6 (IL-6), causing bone resorption. In patients with primary hyperparathyroidism, elevated serum levels of IL-6 normalize after resection of parathyroid tumours. Because IL-6 is also expressed in normal parathyroids and in other endocrine cells (adrenal and islet), we hypothesized that parathyroid tumours might contribute directly to the elevated serum IL-6 levels in patients with hyperparathyroidism. Immunohistochemistry identified IL-6, PTH, and chromogranin-A (an endocrine and neuroendocrine tumour marker) in normal, adenomatous and hyperplastic parathyroids. Using immunofluorescence and confocal microscopy, IL-6 co-localized with PTH and with chromogranin-A in parathyroid cells. All cultured parathyroid tumours secreted IL-6 at levels markedly higher than optimally stimulated peripheral blood mononuclear cells. Supernates from cultured parathyroids stimulated proliferation of an IL-6-dependent cell line, and anti-IL-6 MoAb abolished this stimulatory effect. IL-6 mRNA was documented in cultured parathyroid tumours, cultured normal parathyroids, fresh operative parathyroid tumours and fresh operative normal specimens. In conclusion, these data show that parathyroid tumours and normal parathyroids contain, produce and secrete IL-6. Our findings present a novel pathway by which human parathyroids may contribute markedly to IL-6 production and elevation of serum IL-6 levels in patients with hyperparathyroidism. The physiological relevance of IL-6 production by human parathyroids remains to be determined, but IL-6 secretion by parathyroid tumours may contribute to bone loss and to other multi-system complaints observed in these patients.

Copyright information:

© 2004 Blackwell Publishing Ltd

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