The Thyroid Hormone Receptors Inhibit Hepatic Interleukin-6 Signaling During Endotoxemia

Contreras‐Jurado, Constanza; Alonso-Merino, Elvira; Sáiz-Ladera, Cristina; Valiño, Arturo José; Regadera, Javier; Alemany, Susana; Aranda, Ana

doi:10.1038/srep30990

Cited by 20 publications

(17 citation statements)

References 44 publications

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“…Noteworthy, Signal Transducer and Activator of Transcription 3 (STAT3) activation induced by LPS or IL-6 was inhibited by T3 through TR signaling in RAW 264.7 cells and in primary cultures of BM-derived macrophages. These authors suggested that inhibition of IL-6 signaling induced by T3 has potent regulatory functions during infection and inflammation (72).…”

Section: Introductionmentioning

confidence: 99%

Thyroid Hormone Action on Innate Immunity

Montesinos

Pellizas

2019

Front. Endocrinol.

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The interplay between thyroid hormone action and the immune system has been established in physiological and pathological settings. However, their connection is complex and still not completely understood. The thyroid hormones (THs), 3,3′,5,5′ tetraiodo-L-thyroxine (T4) and 3,3′,5-triiodo-L-thyronine (T3) play essential roles in both the innate and adaptive immune responses. Despite much research having been carried out on this topic, the available data are sometimes difficult to interpret or even contradictory. Innate immune cells act as the first line of defense, mainly involving granulocytes and natural killer cells. In turn, antigen presenting cells, macrophages and dendritic cells capture, process and present antigens (self and foreign) to naïve T lymphocytes in secondary lymphoid tissues for the development of adaptive immunity. Here, we review the cellular and molecular mechanisms involved in T4 and T3 effects on innate immune cells. An overview of the state-of-the-art of TH transport across the target cell membrane, TH metabolism inside these cells, and the genomic and non-genomic mechanisms involved in the action of THs in the different innate immune cell subsets is included. The present knowledge of TH effects as well as the thyroid status on innate immunity helps to understand the complex adaptive responses achieved with profound implications in immunopathology, which include inflammation, cancer and autoimmunity, at the crossroads of the immune and endocrine systems.

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Section: Introductionmentioning

confidence: 99%

Thyroid Hormone Action on Innate Immunity

Montesinos

Pellizas

2019

Front. Endocrinol.

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“…2B) (Tapia et al 1997, 2006, Valencia et al 2004, Fernandez et al 2005, 2007a. Conversely, another study found that T 3 inhibited STAT3 signalling in macrophages after LPS or IL-6 stimulation and had no effect on TNFα induction and NFκB activation in vitro (Contreras-Jurado et al 2016). Both acute and chronic inflammation results in increased liver D2 mRNA expression and activity (Kwakkel et al 2014).…”

Section: Thyroid Hormone Metabolism In Tissue-resident Macrophagesmentioning

confidence: 99%

Thyroid hormone metabolism in innate immune cells

Spek

Fliers

Boelen

2017

Journal of Endocrinology

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Thyroid hormone (TH) metabolism and thyroid status have been linked to various aspects of the immune response. There is extensive literature available on the effects of thyroid hormone on innate immune cells. However, only recently have authors begun to study the mechanisms behind these effects and the role of intracellular TH metabolism in innate immune cell function during inflammation. This review provides an overview of the molecular machinery of intracellular TH metabolism present in neutrophils, macrophages and dendritic cells and the role and effects of intracellular TH metabolism in these cells. Circulating TH levels have a profound effect on neutrophil, macrophage and dendritic cell function. In general, increased TH levels result in an amplification of the pro-inflammatory response of these cells. The mechanisms behind these effects include both genomic and non-genomic effects of TH. Besides a pro-inflammatory effect induced by extracellular TH, the cellular response to pro-inflammatory stimuli appears to be dependent on functional intracellular TH metabolism. This is illustrated by the fact that the deiodinase enzymes and in some cell types also thyroid hormone receptors appear to be crucial for adequate innate immune cell function. This overview of the literature suggests that TH metabolism plays an important role in the host defence against infection through the modulation of innate immune cell function.

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“…Normal circulating T3 levels are essential to maintain myocardial tropism [80] and antiinflammatory effects by reducing peripheral immune cells' recruitment and attenuating the immune system hyperactivation in response to endotoxemia [81]. T3 also reduces macrophage responsiveness to IL-6, suggesting a potential role of T3 replacement in contrasting an exaggerated systemic inflammation, innate immune response, and ultimately cytokine storm [82]. According to this point of view, the low T3 syndrome per se may affect the prognosis of COVID-19 [83] patients as similarly observed in other clinical scenarios [84][85][86][87].…”

Section: Could Medical Management Of Thyroid Diseases Influence the Clinical Course Of Covid-19?mentioning

confidence: 99%

Thyroid and COVID-19: a review on pathophysiological, clinical and organizational aspects

Lisco

Tullio

Jirillo

et al. 2021

J Endocrinol Invest

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Background Thyroid dysfunction has been observed in patients with COVID-19, and endocrinologists are requested to understand this clinical issue. Pandemic-related restrictions and reorganization of healthcare services may affect thyroid disease management. Objective and methods To analyze and discuss the relationship between COVID-19 and thyroid diseases from several perspectives. PubMed/MEDLINE, Google Scholar, Scopus, ClinicalTrial.gov were searched for this purpose by using free text words and medical subject headings as follows: “sars cov 2”, “covid 19”, “subacute thyroiditis”, “atypical thyroiditis”, “chronic thyroiditis”, “hashimoto’s thyroiditis”, “graves’ disease”, “thyroid nodule”, “differentiated thyroid cancer”, “medullary thyroid cancer”, “methimazole”, “levothyroxine”, “multikinase inhibitor”, “remdesivir”, “tocilizumab”. Data were collected, analyzed, and discussed to answer the following clinical questions: “What evidence suggests that COVID-19 may induce detrimental consequences on thyroid function?"; "Could previous or concomitant thyroid diseases deteriorate the prognosis of COVID-19 once the infection has occurred?”; “Could medical management of thyroid diseases influence the clinical course of COVID-19?”; “Does medical management of COVID-19 interfere with thyroid function?”; “Are there defined strategies to better manage endocrine diseases despite restrictive measures and in-hospital and ambulatory activities reorganizations?”. Results SARS-CoV-2 may induce thyroid dysfunction that is usually reversible, including subclinical and atypical thyroiditis. Patients with baseline thyroid diseases are not at higher risk of contracting or transmitting SARS-CoV-2, and baseline thyroid dysfunction does not foster a worse progression of COVID-19. However, it is unclear whether low levels of free triiodothyronine, observed in seriously ill patients with COVID-19, may worsen the disease's clinical progression and, consequently, if triiodothyronine supplementation could be a tool for reducing this burden. Glucocorticoids and heparin may affect thyroid hormone secretion and measurement, respectively, leading to possible misdiagnosis of thyroid dysfunction in severe cases of COVID-19. High-risk thyroid nodules require a fine-needle aspiration without relevant delay, whereas other non-urgent diagnostic procedures and therapeutic interventions should be postponed. Discussion Currently, we know that SARS-CoV-2 could lead to short-term and reversible thyroid dysfunction, but thyroid diseases seem not to affect the progression of COVID-19. Adequate management of patients with thyroid diseases remains essential during the pandemic, but it could be compromised because of healthcare service restrictions. Endocrine care centers should continuously recognize and classify priority cases for in-person visits and therapeutic procedures. Telemedicine may be a useful tool for managing patients not requiring in-person visits.

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The Thyroid Hormone Receptors Inhibit Hepatic Interleukin-6 Signaling During Endotoxemia

Cited by 20 publications

References 44 publications

Thyroid Hormone Action on Innate Immunity

Thyroid Hormone Action on Innate Immunity

Thyroid hormone metabolism in innate immune cells

Thyroid and COVID-19: a review on pathophysiological, clinical and organizational aspects

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