PMID- 34843183
OWN - NLM
STAT- MEDLINE
DCOM- 20220127
LR  - 20230911
IS  - 1473-5598 (Electronic)
IS  - 0263-6352 (Linking)
VI  - 40
IP  - 1
DP  - 2022 Jan 1
TI  - The mineralocorticoid receptor blocker spironolactone lowers plasma interferon-gamma 
      and interleukin-6 in patients with type 2 diabetes and treatment-resistant 
      hypertension.
PG  - 153-162
LID - 10.1097/HJH.0000000000002990 [doi]
AB  - 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-gamma (IFN-gamma), 
      IL-17A, tumor necrosis factor-alpha (TNF-alpha), IL-6, IL-1beta 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-gamma and IL-6 while IL-17A, TNF-alpha, IL-1beta 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-gamma, 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-alpha, IL-6, IL-1beta and IL-10 levels. CONCLUSION: The 
      antihypertensive action of spironolactone in resistant hypertensive patients is 
      associated with suppressed IFN-gamma and IL-6 and not IL-17A. Spironolactone exerts 
      anti-inflammatory actions in vivo on macrophages and T-cells.
CI  - Copyright (c) 2021 Wolters Kluwer Health, Inc. All rights reserved.
FAU - Thangaraj, Sai Sindhu
AU  - Thangaraj SS
AD  - Department of Cardiovascular and Renal Research, Institute of Molecular Medicine, 
      University of Southern Denmark, Odense.
FAU - Oxlund, Christina Stolzenburg
AU  - Oxlund CS
AD  - Department of Cardiology, Hospital of Southwest Jutland, Esbjerg.
FAU - Fonseca, Micaella Pereira Da
AU  - Fonseca MPD
AD  - Department of Cardiovascular and Renal Research, Institute of Molecular Medicine, 
      University of Southern Denmark, Odense.
FAU - Svenningsen, Per
AU  - Svenningsen P
AD  - Department of Cardiovascular and Renal Research, Institute of Molecular Medicine, 
      University of Southern Denmark, Odense.
FAU - Stubbe, Jane
AU  - Stubbe J
AD  - Department of Cardiovascular and Renal Research, Institute of Molecular Medicine, 
      University of Southern Denmark, Odense.
FAU - Palarasah, Yaseelan
AU  - Palarasah Y
AD  - Department of Cancer and Inflammation Research, Institute of Molecular Medicine, 
      University of Southern Denmark.
FAU - Ketelhuth, Daniel F J
AU  - Ketelhuth DFJ
AD  - Department of Cardiovascular and Renal Research, Institute of Molecular Medicine, 
      University of Southern Denmark, Odense.
FAU - Jacobsen, Ib Abildgaard
AU  - Jacobsen IA
AD  - Research Unit for Cardiovascular and Metabolic Prevention, Department of 
      Endocrinology, Odense University Hospital, Odense C, Denmark.
FAU - Jensen, Boye L
AU  - Jensen BL
AD  - Department of Cardiovascular and Renal Research, Institute of Molecular Medicine, 
      University of Southern Denmark, Odense.
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - J Hypertens
JT  - Journal of hypertension
JID - 8306882
RN  - 0 (Angiotensin Receptor Antagonists)
RN  - 0 (Angiotensin-Converting Enzyme Inhibitors)
RN  - 0 (Interleukin-6)
RN  - 0 (Mineralocorticoid Receptor Antagonists)
RN  - 0 (Receptors, Mineralocorticoid)
RN  - 27O7W4T232 (Spironolactone)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Angiotensin Receptor Antagonists
MH  - Angiotensin-Converting Enzyme Inhibitors
MH  - Blood Pressure
MH  - *Diabetes Mellitus, Type 2/drug therapy
MH  - Humans
MH  - *Hypertension/drug therapy
MH  - Interferon-gamma
MH  - Interleukin-6
MH  - Mineralocorticoid Receptor Antagonists
MH  - Receptors, Mineralocorticoid
MH  - Spironolactone
EDAT- 2021/11/30 06:00
MHDA- 2022/01/28 06:00
CRDT- 2021/11/29 15:26
PHST- 2021/11/30 06:00 [pubmed]
PHST- 2022/01/28 06:00 [medline]
PHST- 2021/11/29 15:26 [entrez]
AID - 00004872-202201000-00019 [pii]
AID - 10.1097/HJH.0000000000002990 [doi]
PST - ppublish
SO  - J Hypertens. 2022 Jan 1;40(1):153-162. doi: 10.1097/HJH.0000000000002990.