Assessment of Interleukin-37, the IL-37/TNF-α Ratio, and 8-OHdG as Novel Biomarkers of Oxidative Stress in Iraqi Patients with Hypothyroidism

Abstract

Background: Hypothyroidism is a commonly diagnosed endocrine disorder frequently associated with metabolic disturbances, oxidative stress, and immune dysfunction; growing evidence indicates that inflammation‑related cytokines and oxidative DNA damage contribute to disease progression even in patients receiving thyroid hormone replacement therapy. This study aimed to evaluate serum IL‑37 and TNF‑α and urinary 8‑OHdG levels and to assess the diagnostic and monitoring utility of the IL‑37/TNF‑α ratio by comparing these biomarkers across control, untreated hypothyroid, and post‑treatment groups. Objective: This study aims to examine the relationship between serum levels of IL-37, 8-OHdG, TNF-α, MDA, and the IL37/TNF-α ratio in patients with subclinical hypothyroidism. Methods: The study included 120 individuals divided into three groups: 30 newly diagnosed untreated patients, 30 patients receiving levothyroxine therapy, and 60 healthy controls. Enzyme-linked immunosorbent assay (ELISA) was used to determine serum concentrations of IL-37, TNF-α, MDA, and 8-OHdG. Results: The results revealed that the levels of TNF-α, MDA, and 8-OHdG of the untreated hypothyroid group were significantly higher than those of both the treated and control groups. In contrast, IL-37 levels were significantly decreased, leading to a marked decrease in the IL-37/TNF-α ratio. The results exhibited significant improvement in inflammatory markers, with partial restoration of IL-37 levels and the IL-37/TNF-α ratio for those patients who are receiving levothyroxine therapy. In addition, MDA and 8-OHdG levels remained significantly higher in patients receiving levothyroxine than those observed in healthy controls. Conclusions: The findings indicate that, in hypothyroid subjects receiving prolonged hormone therapy, persistent oxidative DNA damage and elevated proinflammatory cytokine levels were observed. Measuring the levels of IL-37, 8-OHdG, and the IL-37/TNF-α ratio may be valuable adjunctive laboratory tests when assessing for inflammatory response, monitoring treatment effectiveness, and facilitating better insight into the underlying pathophysiologic mechanisms associated with subclinical hypothyroidism.