Th1 polarization and low-T3 syndrome are correlated with hyperleptinemia in hemodialysis patients

Patients undergoing chronic hemodialysis (HD) have an impaired immune response with a dysregulated Th1/Th2 cytokine network and altered the levels of thyroid hormone (TH) in euthyroid sick syndrome. Leptin, an adipocyte-secreted hormone, is considered to be a proinflammatory adipocytokine, with multiple effects on several tissues acting on the intermediate and energy metabolism. The aims of the present study were to assess the changes in serum levels of leptin and their correlation with Th1/Th2 cytokine and TH production in HD patients.

Fifty-three uremic patients with hemodialysis were evaluated; 30 healthy volunteers served as controls. Baseline serum concentrations of interleukin-2 (IL-2), sIL-2R, interferon-gamma (IFN-gamma), IL-4 and IL-10 were analyzed using ELISA. Serum levels of leptin, total triiodothyronine (TT3), free triiodothyronine (FT3), total thyroxine (TT4), free thyroxine (FT4) and thyroid-stimulating hormone (TSH) were determined by radioimmunoassay (RIA). Other metabolic variables were measured in all patients and control subjects. Multiple correlation analysis was performed among variables.

Mean serum leptin concentration was significantly higher in HD patients than that in controls (p<0.01), especially in women (p<0.001). While the fasting serum levels of sIL-2R and Th1-type cytokines including IL-2 and IFN-gamma were significantly higher in HD patients compared with controls, Th2-type cytokine, including IL-4 and IL-10, levels did not differ between patients and controls. The serum TT3 and FT3 levels were lower in patients than controls, but TT4, FT4 and TSH were no different. Serum leptin levels in HD patients were significantly positively correlated with IL-2, IFN-gamma, sIL-2R and TSH; and negatively correlated with IL-4, IL-10, TT3 and FT3. Serum IL-2 levels correlated positively with serum IL-4, sIL-2R, TT3 and FT3. A negative correlation was observed between serum IFN-gamma and IL-4 levels in the patients.

These data suggest that hyperleptinemia in HD patients correlated with cytokine dysregulation with a high level of Th1-type cytokines, and euthyroid sick syndrome with low T3 levels which might be involved in Th1 polarization and low-T3 syndrome in dialysis patients.