Primary Aldosteronism Can Alter Peripheral Levels of Transforming Growth Factor β and Tumor Necrosis Factor α

Primary aldosteronism (PA) is the most common secondary cause of hypertension that has recently been implicated in alterations of the immune system and progression of cardiovascular disease. The objective was to study the cytokines transforming growth factor β1 (TGF-β1), tumor necrosis factor α (TNF-α), and interleukin 10 (IL-10) in patients with PA and essential hypertensives (EH) and evaluate its association with the renin-angiotensin-aldosterone system. We studied 26 PA and 52 EH patients as controls, adjusted by their blood pressure, body mass index, age, and gender. In both groups, PA and EH, we measured serum aldosterone (SA), plasma renin activity (PRA), and cytokines TGF-β1, TNF-α, and IL-10. In addition, 17 PA patients were treated for 6 months with spironolactone, a mineralocorticoid receptor (MR) antagonist. PA patients had lower levels of TGF-β1 (17.6±4.1 vs 34.5±20.5 pg/ml, p<0.001) and TNF-α (17.0±4.4 vs 35.6±21.7 pg/ml, p<0.001) and similar IL-10 levels (99.7±18.7 vs 89.4±49.5 pg/ml, p: ns), as compared with EH controls. TGF-β1 and TNF-α levels showed a remarkable correlation with SA/PRA ratio in the total group (PA+EH). The treatment of PA patients with spironolactone increased the TGF-β1 levels (18.3±5.9 to 28.4±6.3 pg/ml, p<0.001), while TNF-α, and IL-10 remained unchanged. Our results showed that PA patients have lower TGF-β1 and TNF-α cytokine serum levels than EH. TGF-β1 levels were restored with spironolactone, showing a MR-dependent regulation. In this way, the chronic aldosterone excess modifies the TGF-β1 levels, which could produce an imbalance in the immune system homeostasis that may promote an early proinflammatory cardiovascular phenotype.