Thyroid hormones act as modulators of inflammation through their nuclear receptors

Abstract

Reciprocal crosstalk between endocrine and immune systems has been well-documented both in physiological and pathological conditions, although the connection between the immune system and thyroid hormones (THs) remains largely unclear. Inflammation and infection are two important processes modulated by the immune system, which have profound effects on both central and peripheral THs metabolism. Conversely, optimal levels of THs are necessary for the maintenance of immune function and response. Although some effects of THs are mediated by their binding to cell membrane integrin receptors, triggering a non-genomic response, most of the actions of these hormones involve their binding to specific nuclear thyroid receptors (TRs), which generate a genomic response by modulating the activity of a great variety of transcription factors. In this special review on THs role in health and disease, we highlight the relevance of these hormones in the molecular mechanisms linked to inflammation upon their binding to specific nuclear receptors. In particular, we focus on THs effects on different signaling pathways involved in the inflammation associated with various infectious and/or pathological processes, emphasizing those mediated by NF-kB, p38MAPK and JAK/STAT. The findings showed in this review suggest new opportunities to improve current therapeutic strategies for the treatment of inflammation associated with several infections and/or diseases, such as cancer, sepsis or Covid-19 infection.

Clinical and Pathophysiologic Insights of Free triiodothyronine/Free thyroxine Ratio in Patients with Heart Failure with Preserved Ejection Fraction: Data from the NETDiamond Cohort

“…Furthermore, it reduces T3 availability due to the influence of cytokines on deiodinases’ activity [4]. On the other hand, THs modulate several immune responses and are thought to promote anti-inflammatory responses at physiological levels [14]. In our study, we found that lower levels of FT3/FT4 ratio and FT3 were associated with higher ESR levels, suggesting a stronger inflammatory response with lower levels of FT3.…”

The Relationship Between Toxoplasmosis and Concentration of Prolactin and Progesterone in Pregnant Women

“…Prolactin strongly elicits innate and adaptive immune responses, by promoting the maturation of Clusters of Differentiation 4 (CD4), and CD8 on surfaces of immune cells including monocytes, T helper cells, macrophages and dendritic cells, into CD4+ and CD8+ cells. Furthermore, serum prolactin levels (PRL) can alter Th1 and Th2 type cytokine production to favor interleukin (IL)-6 and interferongamma (INF-γ) secretion and also enhance immunoglobulin (Ig) production [25][26] . This could explain why pregnant women generally have weaker immunity compared to their non-pregnant counterparts.…”

Supplementation with selenium and coenzyme Q10 in an elderly Swedish population low in selenium — positive effects on thyroid hormones, cardiovascular mortality, and quality of life

“…Gu et al reported in their study, which included more than 3100 patients comprising more than 7700 patient-years, an increased risk for carotid atherosclerosis related to low-grade systemic inflammation [ 36 ]. Lasa and Contreras-Jurado argued in their review, that one explanation for this association could be the modulating function of thyroid hormones on inflammatory pathways, through their binding to specific nuclear thyroid receptors, all pointing to the close association between the thyroid hormones and inflammation [ 37 ]. This concurs with our finding of higher CRP concentration in the group with the lowest fT3 levels.…”