Thyroid Hormones Interaction With Immune Response, Inflammation and Non-thyroidal Illness Syndrome

Abstract

The interdependence between thyroid hormones (THs), namely, thyroxine and triiodothyronine, and immune system is nowadays well-recognized, although not yet fully explored. Synthesis, conversion to a bioactive form, and release of THs in the circulation are events tightly supervised by the hypothalamic–pituitary–thyroid (HPT) axis. Newly synthesized THs induce leukocyte proliferation, migration, release of cytokines, and antibody production, triggering an immune response against either sterile or microbial insults. However, chronic patho-physiological alterations of the immune system, such as infection and inflammation, affect HPT axis and, as a direct consequence, THs mechanism of action. Herein, we revise the bidirectional crosstalk between THs and immune cells, required for the proper immune system feedback response among diverse circumstances. Available circulating THs do traffic in two distinct ways depending on the metabolic condition. Mechanistically, internalized THs form a stable complex with their specific receptors, which, upon direct or indirect binding to DNA, triggers a genomic response by activating transcriptional factors, such as those belonging to the Wnt/β-catenin pathway. Alternatively, THs engage integrin αvβ3 receptor on cell membrane and trigger a non-genomic response, which can also signal to the nucleus. In addition, we highlight THs-dependent inflammasome complex modulation and describe new crucial pathways involved in microRNA regulation by THs, in physiological and patho-physiological conditions, which modify the HPT axis and THs performances. Finally, we focus on the non-thyroidal illness syndrome in which the HPT axis is altered and, in turn, affects circulating levels of active THs as reported in viral infections, particularly in immunocompromised patients infected with human immunodeficiency virus.

Inhibition by Thyroid Hormones of Cell Migration Activated by IGF-1 and MCP-1 in THP-1 Monocytes: Focus on Signal Transduction Events Proximal to Integrin αvβ3

“…In fact, after long-term treatment with thyroxine, there is an induction of apoptosis of T lymphoma cells through an increase of oxidative stress species from iNOS activity (Barreiro Arcos et al, 2013). The increase of ROS by NADPH oxidase and mitochondrial ROS activated the first and NO production by cytokines and downstream signaling including PI3K-Akt axis, but also the MAPK pathway and STAT-1α activation are among the first steps leading to Nodlike receptor protein 3 (NLRP3) inflammasome activation, giving rise to physiological responses aimed for bactericidal clearance, cell survival, and an anti-inflammatory condition (De Luca et al, 2021).…”

Das gestresste Immunsystem und Autoimmunität

“…Auch der Zusammenhang zwischen psychologischem Stress und Aktivierung der HHN wurde in diesem Zeitraum bereits beschrieben [6,7]. Neben der HHN-Achse werden auch viele weitere Hormonsysteme, wie die Produktion von Sexualhormonen, Schilddrüsenhormone oder die Bauchspeicheldrüse durch Stress moduliert und auch diese Hormone sind in der Lage wiederum Immunzellen über entsprechende Rezeptoren direkt in ihrer Funktion zu beeinflussen [8][9][10][11].…”

Influence of Thyroid Hormones and Cortisol on Immune Response in Case of Children’s Bronchopulmonary Diseases

“…By severe and prolonged diseases, biochemical reactions are inhibited, and thyroid hormones fall in blood serum [6,13,30,63,94]. The primary disease severity correlates directly with such changes [6,23,52,55]. Simultaneously, hypothyroidism and thyrotoxicosis are not traced clinically [23].…”

“…Such an adaptive response is called a euthyroid sick syndrome. There are some other names in literature sources: non-thyroidal disease syndrome, thyroid pseudo-dysfunction syndrome, euthyroid patient syndrome, euthyroid pathological syndrome [6,29,36,52,55,64,106]. It is caused by various diseases (infectious, inflammatory, traumatic, neoplastic ones) by no concomitant thyroid pathology and its integrity.…”

“…It is caused by various diseases (infectious, inflammatory, traumatic, neoplastic ones) by no concomitant thyroid pathology and its integrity. In literature, the euthyroid sick syndrome is described in adult acute bronchitis [6,52,55].…”