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

Endocrine Connections

Korcan Demir¹  A S Paul van Trotsenburg²  Saskia Aan²  Olga V Surovtseva²  Anne H van der Spek²  Timo K van den Berg²  Anja L M van Gucht³  Annemarie van de Geer⁴  Anton T J Tool⁴ 

[1] Division of Pediatric Endocrinology, Dokuz Eylül University, Izmir, Turkey;Department of Endocrinology and Metabolism, Academic Medical Center, Amsterdam, The Netherlands;Department of Endocrinology, Erasmus Medical Center, Rotterdam, The Netherlands;Sanquin Research and Landsteiner Laboratory, Academic Medical Center, Amsterdam, The Netherlands;

关键词: thyroid hormone receptor alpha;    resistance to thyroid hormone;    interleukin-8;    macrophage;    innate immunity;   

DOI  :  10.1530/EC-17-0213

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown