The mineralocorticoid receptor blocker spironolactone lowers plasma interferon-γ and interleukin-6 in patients with type 2 diabetes and treatment-resistant hypertension.

Abstract

BACKGROUND:

The mineralocorticoid receptor antagonist spironolactone lowers blood pressure in patients with resistant hypertension despite antihypertensive treatment with angiotensin-converting inhibitors (ACEi) and angiotensin-II receptor blockers (ARB). In preclinical studies, spironolactone suppresses pro-hypertensive interleukin 17A (IL-17A).

OBJECTIVES:

Plasma samples were analysed from a randomized, double-blind placebo-controlled trial with spironolactone given to patients with type 2 diabetes mellitus (T2DM) and resistant hypertension on three antihypertensive drugs. We tested the hypothesis that spironolactone-induced antihypertensive effects are associated with suppression of IL-17A and related cytokines.

METHODS:

Interferon-γ (IFN-γ), IL-17A, tumor necrosis factor-α (TNF-α), IL-6, IL-1β and IL-10 were assessed in plasma with immunoassay in samples before and after 16 weeks of treatment with placebo or spironolactone (12.5-25-50 mg/day).

RESULTS:

Spironolactone significantly reduced plasma IFN-γ and IL-6 while IL-17A, TNF-α, IL-1β and IL-10 were unchanged. IL-6 was more sensitive to higher doses of spironolactone. At baseline, serum aldosterone correlated positively with diastolic night blood pressure. Urine albumin/creatinine-ratios correlated positively with plasma IL-6 at baseline. There were no relations between aldosterone and cytokine concentrations at baseline; between cytokine concentration and blood pressure at baseline; and between cytokine concentration decrease and blood pressure decrease, except for IFN-γ, after treatment. The spironolactone-induced elevation in plasma potassium related inversely to blood pressure but not to changes in cytokines. In macrophages in vitro, spironolactone suppressed lipopolysaccharide (LPS)-induced TNF-α, IL-6, IL-1β and IL-10 levels.

CONCLUSION:

The antihypertensive action of spironolactone in resistant hypertensive patients is associated with suppressed IFN-γ and IL-6 and not IL-17A. Spironolactone exerts anti-inflammatory actions in vivo on macrophages and T-cells.

• Authors: Sai Sindhu Thangaraj, Christina Stolzenburg Oxlund, Micaella Pereira Da Fonseca, Per Svenningsen, Jane Stubbe, Yaseelan Palarasah, Daniel F J Ketelhuth, Ib Abildgaard Jacobsen, Boye L Jensen
• Journal: Journal of hypertension (J Hypertens) Vol. 40 Issue 1 Pg. 153-162 (01 01 2022) ISSN: 1473-5598 [Electronic] Netherlands
• PMID: 34843183 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

Chemical References

• Angiotensin Receptor Antagonists
• Angiotensin-Converting Enzyme Inhibitors
• Interleukin-6
• Mineralocorticoid Receptor Antagonists
• Receptors, Mineralocorticoid
• Spironolactone
• Interferon-gamma

Topics

• Angiotensin Receptor Antagonists
• Angiotensin-Converting Enzyme Inhibitors
• Blood Pressure
• Diabetes Mellitus, Type 2 (drug therapy)
• Humans
• Hypertension (drug therapy)
• Interferon-gamma
• Interleukin-6
• Mineralocorticoid Receptor Antagonists
• Receptors, Mineralocorticoid
• Spironolactone