Increased circulating interleukin-8 in patients with resistance to thyroid hormone receptor α

Anne H. van Der Spek, Olga V. Surovtseva, Saskia Aan, Anton T.J. Tool, Annemarie van de Geer, Korcan Demir, Anja L.M. van Gucht, A. S.Paul van Trotsenburg, Timo K. van den Berg, Eric Fliers, Anita Boelen*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Innate immune cells have recently been identified as novel thyroid hormone (TH) target cells in which intracellular TH levels appear to play an important functional role. The possible involvement of TH receptor alpha (TRα), which is the predominant TR in these cells, has not been studied to date. Studies in TRα0/0 mice suggest a role for this receptor in innate immune function. The aim of this study was to determine whether TRα affects the human innate immune response. We assessed circulating interleukin-8 concentrations in a cohort of 8 patients with resistance to TH due to a mutation of TRα (RTHα) and compared these results to healthy controls. In addition, we measured neutrophil and macrophage function in one of these RTHα patients (mutation D211G). Circulating interleukin-8 levels were elevated in 7 out of 8 RTHα patients compared to controls. These patients harbor different mutations, suggesting that this is a general feature of the syndrome of RTHα. Neutrophil spontaneous apoptosis, bacterial killing, NAPDH oxidase activity and chemotaxis were unaltered in cells derived from the RTHαD211G patient. RTHα macrophage phagocytosis and cytokine induction after LPS treatment were similar to results from control cells. The D211G mutation did not result in clinically relevant impairment of neutrophil or pro-inflammatory macrophage function. As elevated circulating IL-8 is also observed in hyperthyroidism, this observation could be due to the high-normal to high levels of circulating T3 found in patients with RTHα.

Original languageEnglish
Pages (from-to)731-740
Number of pages10
JournalEndocrine Connections
Issue number8
Publication statusPublished - 1 Nov 2017

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