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Updated: Jun 12, 2025
Isolation and Adoptive Transfer of High Salt Treated Antigen-presenting Dendritic Cells
Published on: March 5, 2019
Recent advancements in targeting the immune system to treat hypertension
Rikeish R Muralitharan1, Francine Z Marques2, Joanne A O'Donnell3
1Hypertension Research Laboratory, School of Biological Sciences, Monash University, Melbourne, VIC, Australia; Victorian Heart Institute, Monash University, Clayton, Australia.
Insights
High blood pressure (hypertension) affects over a billion adults globally. New research explores targeting the immune system and inflammation to develop novel therapies for better blood pressure control.
Area of Science:
- Immunology
- Cardiovascular Medicine
- Pharmacology
Background:
- Hypertension is a leading global cause of death, with over 1.3 billion adults affected, particularly in low- and middle-income countries.
- A significant portion of individuals with hypertension have uncontrolled blood pressure, increasing their risk of cardiovascular events due to challenges in diagnosis, treatment, and therapeutic response.
- Current therapies, including monotherapy and combination treatments, often fail to achieve target blood pressure levels, necessitating the development of new therapeutic strategies.
Purpose of the Study:
- To review the intricate role of the immune system in hypertension development and regulation.
- To evaluate existing clinical trials investigating anti-inflammatory agents and cytokine blockade for hypertension management.
- To identify knowledge gaps in preclinical and clinical data and propose future directions for immune-targeted hypertension therapies.
Main Methods:
- Review of scientific literature on the immune system's involvement in hypertension.
- Analysis of clinical trial data for anti-inflammatory drugs (colchicine, methotrexate) and cytokine inhibitors (IL-1β, TNF-α).
- Exploration of novel therapeutic targets, including isolevuglandins and short-chain fatty acids.
Main Results:
- The immune system, through inflammation, plays a critical role in blood pressure regulation and hypertension development.
- Clinical trials targeting inflammation, such as those using colchicine, methotrexate, IL-1β, and TNF-α blockade, show potential but require further investigation.
- Emerging strategies involve targeting specific immune components like isolevuglandins and utilizing gut microbiome-derived short-chain fatty acids for their anti-inflammatory and blood pressure-lowering effects.
Conclusions:
- Targeting specific immune system pathways offers a promising avenue for developing novel hypertension therapies.
- Isolevuglandins and short-chain fatty acids represent potential targets for future drug development and lifestyle interventions.
- Modulating the immune system could lead to improved medication adherence and better blood pressure control, reducing adverse events.
Abstract:
Hypertension is the key leading risk factor for death globally, affecting ∼1.3 billion adults, particularly in low- and middle-income countries. Most people living with hypertension have uncontrolled high blood pressure, increasing their likelihood of cardiovascular events. Significant issues preventing blood pressure control include lack of diagnosis, treatment, and response to existing therapy. For example, monotherapy and combination therapy are often unable to lower blood pressure to target levels. New therapies are urgently required to tackle this issue, particularly those that target the mechanisms behind hypertension instead of treating its symptoms. Acting via an increase in systemic and tissue-specific inflammation, the immune system is a critical contributor to blood pressure regulation and is considered an early mechanism leading to hypertension development. Here, we review the immune system's role in hypertension, evaluate clinical trials that target inflammation, and discuss knowledge gaps in pre-clinical and clinical data. We examine the effects of anti-inflammatory drugs colchicine and methotrexate on hypertension and evaluate the blockade of pro-inflammatory cytokines IL-1β and TNF-α on blood pressure in clinical trials. Lastly, we highlight how we can move forward to target specific components of the immune system to lower blood pressure. This includes targeting isolevuglandins, which accumulate in dendritic cells to promote T cell activation and cytokine production in salt-induced hypertension. We discuss the potential of the dietary fibre-derived metabolites short-chain fatty acids, which have anti-inflammatory and blood pressure-lowering effects via the gut microbiome. This would limit adverse events, leading to improved medication adherence and better blood pressure control.
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