Immune-modulating therapies for hypertension
Given the high failure rate of current drug therapies for patients with hypertension, it is time to consider the involvement of alternative pathways in this disease. Recent evidence provides strong support for a role of the immune system in the development of hypertension and suggests that clinical trials to evaluate the efficacy of immune-targeted therapies should be advanced as a priority.
Hypertension affects 30% of adults and is the leading risk factor for major cardiovascular events (such as heart attack and stroke), chronic kidney disease, cognitive impairment and dementia. Hypertension is the main contributor to mortality and disability, far outweighing other genetic, occupational, environmental and lifestyle factors. However, up to 40% of patients with hypertension fail to achieve healthy blood pressure targets, even when prescribed a combination of drugs from three or more classes of current antihypertensive medications, and more than 20 years have now passed since any new class of antihypertensive medication has entered the market.
A review article published in Nature Reviews Immunology by Grant Drummond and colleagues summarizes the clinical and experimental evidence supporting a contribution of immune mechanisms to the development of hypertension. In particular, they highlight the immune cell subsets that are postulated to either promote or protect against hypertension through modulation of cardiac output and/or peripheral vascular resistance.
Importantly, there is a wealth of evidence from animal studies that clinically approved T cell-modulating agents, such as mycophenolate mofetil (an immunosuppressant used in organ transplant recipients) and anti-TNF treatments (used for rheumatoid arthritis), are highly effective at lowering blood pressure in both male and female animals. Given this knowledge, the authors ask why there seems to be a reluctance to use immune-targeted approaches to treat primary hypertension in humans. They provide a critical appraisal of the issues that remain to be addressed in order that clinical hypertension might be effectively managed as an immune and/or inflammatory disorder.