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Interleukin-6 production and secretion by human parathyroids.
S A Safley1, F Villinger, E H Jackson
1Department of Surgery, Emory University School of Medicine, Atlanta, Georgia, USA. ssafley@emory.edu
Clinical and Experimental Immunology
|March 20, 2004
Summary
Parathyroid tumors and normal parathyroids produce and secrete interleukin-6 (IL-6). This finding suggests a new way parathyroids contribute to high IL-6 levels in hyperparathyroidism, potentially worsening bone loss.
Area of Science:
- Endocrinology
- Immunology
- Oncology
Background:
- Parathyroid hormone (PTH) stimulates IL-6 production, leading to bone resorption.
- Elevated serum IL-6 in hyperparathyroidism normalizes post-surgery, suggesting parathyroid involvement.
- IL-6 is present in normal parathyroids and other endocrine cells.
Purpose of the Study:
- To investigate if parathyroid tumors directly contribute to elevated serum IL-6 levels in hyperparathyroidism.
- To determine the presence, production, and secretion of IL-6 by parathyroid tissues.
Main Methods:
- Immunohistochemistry to detect IL-6, PTH, and chromogranin-A in parathyroid tissues.
- Immunofluorescence and confocal microscopy to assess co-localization of IL-6 with PTH and chromogranin-A.
- In vitro culture of parathyroid tumors and normal parathyroids to measure IL-6 secretion and mRNA expression.
Main Results:
- IL-6, PTH, and chromogranin-A were identified in normal, adenomatous, and hyperplastic parathyroids.
- IL-6 co-localized with PTH and chromogranin-A in parathyroid cells.
- Cultured parathyroid tumors secreted significantly higher IL-6 levels than stimulated peripheral blood mononuclear cells.
- Parathyroid supernates stimulated an IL-6-dependent cell line, an effect abolished by anti-IL-6 antibody.
- IL-6 mRNA was detected in both tumorous and normal parathyroid tissues.
Conclusions:
- Parathyroid tumors and normal parathyroids contain, produce, and secrete IL-6.
- This represents a novel mechanism contributing to elevated serum IL-6 in hyperparathyroidism.
- IL-6 secretion by parathyroid tumors may play a role in bone loss and other patient symptoms.