Keywords
low triiodothyronine syndrome
glucocorticoids
thyroid hormones
phagocytes
immunometabolism
How to Cite
Abstract
In press
Background. The acute phase of inflammation is accompanied by profound reprogramming of neuroendocrine regulation involving the Hypothalamic–Pituitary–Adrenal (HPA) and Hypothalamic–Pituitary–Thyroid (HPT) axes. Increased cortisol levels and decreased triiodothyronine reflect interconnected components of immunometabolic adaptation aimed at meeting the energy demands of innate immunity; however, the integration of systemic and tissue-level mechanisms underlying this response remains insufficiently defined.
Aim. To propose an integrative model of HPA–HPT axis interaction as a unified cytokine-mediated immunometabolic regulatory complex of the acute phase of inflammation, encompassing both systemic and cellular levels of regulation.
Materials and Methods. A narrative review of experimental, clinical, and review studies (1998–2025) indexed in PubMed, Scopus, ScienceDirect, EMBASE, MEDLINE, the Cochrane Library, and Google Scholar was conducted. The selection was based on the following keywords: low triiodothyronine syndrome, glucocorticoids, thyroid hormones, cytokines, phagocytes, immunometabolism. The research was conducted as a private initiative of the authors, without grant funding and state registration of the topic.
Research Ethics. Only those sources were selected for analysis whose authors clearly adhered to modern bioethical norms when conducting their research.
Results. During the acute phase of inflammation, coordinated activation of the HPA axis ensures mobilization of energy substrates, while remodeling of the HPT axis contributes to their functional redistribution in favor of effector mechanisms of innate immunity. Glucocorticoids modulate the intensity and spatial organization of the inflammatory response, whereas local action of thyroid hormones in phagocytes, particularly via deiodinase-dependent mechanisms, determines their metabolic phenotype and bactericidal activity. In this context, Low Triiodothyronine Syndrome (LT3S) emerges as a component of adaptive immunometabolic reprogramming relevant to the phagocytic phase of inflammation. Disruption of coordination between the axes leads to allostatic overload.
Conclusions. Immunometabolic adaptation in the acute phase of inflammation is formed through the function of a unified cytokine-mediated regulatory complex involving the HPA and HPT axes at both systemic and cellular levels. LT3S reflects not an isolated thyroid dysfunction but an adaptive redistribution of resources and regulation of immune function, including the bactericidal activity of phagocytes, supporting the need for integrative approaches to the assessment of neuroendocrine changes.
Keywords: endocrinology, low triiodothyronine syndrome, glucocorticoids, thyroid hormones, phagocytes, immunometabolism.
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