Related Experiment Video
Updated: Jun 20, 2026
Isolation and Adoptive Transfer of High Salt Treated Antigen-presenting Dendritic Cells
Published on: March 5, 2019
Candesartan reduces the innate immune response to lipopolysaccharide in human monocytes
Ignacio M Larrayoz1, Tao Pang, Julius Benicky
1Section on Pharmacology, Division of Intramural Research Programs, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA.
Insights
Candesartan, an angiotensin II receptor type 1 blocker, reduces the innate immune response to bacterial lipopolysaccharide (LPS) in human monocytes. These anti-inflammatory effects may extend beyond hypertension to other inflammatory conditions.
Area of Science:
- Immunology
- Pharmacology
- Cardiovascular Medicine
Background:
- Angiotensin II receptor type 1 (AT1) inhibition is known to reduce chronic inflammation in hypertension.
- The effect of AT1 receptor inhibition on the acute innate inflammatory response to bacterial lipopolysaccharide (LPS) is not well understood.
Purpose of the Study:
- To investigate whether AT1 receptor inhibition by candesartan modulates the innate inflammatory response of human monocytes to LPS.
- To explore potential mechanisms underlying candesartan's anti-inflammatory effects in monocytes.
Main Methods:
- Human monocytes were isolated and incubated with LPS in the presence or absence of candesartan.
- Gene expression of inflammatory markers (CD14, TNF-α, IL-1β, IL-6) and receptor binding were analyzed.
- Cytokine release, NF-κB pathway activation, and reactive oxygen species (ROS) formation were measured.
Main Results:
- Human monocytes lacked detectable AT1 receptors and did not respond to angiotensin II.
- Candesartan significantly reduced LPS-induced expression of CD14, TNF-α, IL-1β, IL-6, and LOX-1 mRNAs.
- Candesartan attenuated LPS-induced NF-κB activation, TNF-α and IL-6 secretion, and ROS production, without affecting IL-10 secretion.
Conclusions:
- The anti-inflammatory effects of candesartan on monocytes exposed to LPS appear to be independent of AT1 receptor blockade.
- Candesartan effectively suppresses the innate immune response to LPS in human monocytes.
- These findings suggest potential therapeutic applications for candesartan in inflammatory disorders beyond hypertension.
Objective:
Inhibition of angiotensin II receptor type 1 (AT1) reduces chronic inflammation associated with hypertension. We asked whether AT1 receptor inhibition would reduce the innate inflammatory response induced by bacterial lipopolysaccharide (LPS).
Methods:
We used unstimulated human circulating monocytes obtained from healthy donors by counterflow centrifugal elutriation. Monocytes were studied in vitro after incubation with LPS (50 ng/ml) with and without 1 mumol/l candesartan, an AT1 receptor blocker. Angiotensin II receptor mRNA expression was determined by reverse transcriptase-PCR and receptor binding by autoradiography; inflammatory factor mRNA expression was studied by reverse transcriptase-PCR and cytokine release by ELISA.
Results:
Human monocytes did not express detectable AT1 receptors, and angiotensin II did not induce inflammatory factor mRNA expression or cytokine release. However, candesartan substantially reduced the LPS-induced expression of the mRNAs for the LPS recognition protein cluster of differentiation 14, the proinflammatory cytokines tumor necrosis factor alpha, interleukin-1 beta and interleukin-6 and the lectin-like oxidized low-density lipoprotein receptor. In addition, candesartan reduced the activation of the nuclear factor kappa B pathway, the tumor necrosis factor alpha and interleukin-6 secretion, and the ROS formation induced by LPS, without affecting the secretion of interleukin-10.
Conclusion:
We hypothesize that the anti-inflammatory effects of candesartan in these cells are likely mediated by mechanisms unrelated to AT1 receptor blockade. Our results demonstrate that candesartan significantly reduces the innate immune response to LPS in human circulating monocytes. The anti-inflammatory effects of candesartan may be of importance not only in hypertension but also in other inflammatory disorders.
Related Concept Videos
01:30Antihypertensive Drugs: Angiotensin II Receptor Blockers
01:22Dose-Response Relationship: Potency and Efficacy
01:25Antihypertensive Drugs: Direct Renin Inhibitors
01:26Heart Failure Drugs: Inhibitors of Renin-Angiotensin System
01:30Antihypertensive Drugs: Angiotensin-Converting Enzyme Inhibitors