Cross-Talk between the Cytokine IL-37 and Thyroid Hormones in Modulating Chronic Inflammation Associated with Target Organ Damage in Age-Related Metabolic and Vascular Conditions

Abstract

Chronic inflammation is considered to be the main mechanism contributing to the development of age-related metabolic and vascular conditions. The phases of chronic inflammation that mediate the progression of target organ damage in these conditions are poorly known, however. In particular, there is a paucity of data on the link between chronic inflammation and metabolic disorders. Based on some of our own results and recent developments in our understanding of age-related inflammation as a whole-body response, we discuss the hypothesis that cross-talk between the cytokine IL-37 and thyroid hormones could be the key regulatory mechanism that justifies the metabolic effects of chronic tissue-related inflammation. The cytokine IL-37 is emerging as a strong natural suppressor of the chronic innate immune response. The effect of this cytokine has been identified in reversing metabolic costs of chronic inflammation. Thyroid hormones are known to regulate energy metabolism. There is a close link between thyroid function and inflammation in elderly individuals. Nonlinear associations between IL-37 and thyroid hormones, considered within the wider clinical context, can improve our understanding of the phases of chronic inflammation that are associated with target organ damage in age-related metabolic and vascular conditions.

Association between serum Klotho levels and hypothyroidism in older adults: NHANES 2007–2012

“…On the one hand, under aging conditions, changes in tissue structure gradually accumulate towards malignant transformation, leading to increased vascular permeability and extravasation 31 . These changes slow down the transport efficiency of thyroid hormones in the vascular bed and affect their ability to pass through the endothelial barrier 32 . On the other hand, the aging process results in a decrease in the production of thyroid hormones 33 , 34 .…”

A Critical Appraisal of the Diagnostic and Prognostic Utility of the Anti-Inflammatory Marker IL-37 in a Clinical Setting: A Case Study of Patients with Diabetes Type 2

“…According to both our results ( Table 3 , the regression model “C”) and the literature evidence, the frailty status is able to modify correlations between TSH and IL-37. In our recently published review paper, we elaborated the role of TSH—a sign of the activated hypothalamus-pituitary-thyroid (HPT) axis—in conditions associated with inflammation and impaired glucose-related metabolism, such as aging and cardio-metabolic conditions [ 81 ]. In brief, a hypothyroid state in older individuals, indicated by increased TSH, is viewed as the system’s homeostatic reaction which takes place when IL-37, as a major tissue homeostatic mechanism under inflammatory conditions, fails to restore the metabolic costs of inflammation.…”

Thyroid hormone sensitivity and diabetes onset: a longitudinal cross-lagged cohort

“…Studies have shown that people with abnormal glucose metabolism have high levels of inflammatory cytokines ( 44 ). The crosstalk between the cytokine IL-37 and thyroid hormones could be the key regulatory mechanism that justifies the glucose metabolic effects ( 45 ). The exact pathophysiological mechanism of glucose metabolism on thyroid hormones resistance needs further research.…”