Hypertension: a new treatment for an old disease? Targeting the immune system

Abstract

Arterial hypertension represents a serious public health problem, being a major cause of morbidity and mortality worldwide. The availability of many antihypertensive therapeutic strategies still fails to adequately treat around 20% of hypertensive patients, who are considered resistant to conventional treatment. In the pathogenesis of hypertension, immune system mechanisms are activated and both the innate and adaptive immune responses play a crucial role. However, what, when and how the immune system is triggered during hypertension development is still largely undefined. In this context, this review highlights scientific advances in the manipulation of the immune system in order to attenuate hypertension and end-organ damage. Here, we discuss the potential use of immunosuppressants and immunomodulators as pharmacological tools to control the activation of the immune system, by non-specific and specific mechanisms, to treat hypertension and improve end-organ damage. Nevertheless, more clinical trials should be performed with these drugs to establish their therapeutic efficacy, safety and risk-benefit ratio in hypertensive conditions. LINKED ARTICLES: This article is part of a themed section on Immune Targets in Hypertension. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.12/issuetoc.

Figure 1

Targets in the immune system for the treatment of hypertension. The unregulated and persistent activation of the immune system, cytokine release and oxidative stress induce cardiovascular organ damage and, consequently, hypertension. Drugs available to modulate the immune response and likely to control BP and improve end‐organ damage are shown in the grey boxes. The dashed orange arrows indicate a diminished response, while black arrows indicate activated mechanisms. More details about the drugs are found in the main text. Based on patient risk/benefit ratio profile of targeted therapies, immune system modulation may provide a new strategy to treat hypertension. AP‐1, activator protein 1; IRF3, IFN regulatory factor 3; MyD88, myeloid differentiation response 88 protein; Tac, tacrolimus; TRIF, toll/IL‐1 receptor homologous region domain‐containing adapter‐inducing IFN‐β.

Figure 2

Differential effects of immunosuppressants and immunomodulators on hypertension. Classical immunosuppressant drugs are in the green section, immunomodulators targeting the innate immune response are in the yellow section and immunomodulators targeting the adaptive immune response are in the red section. Drugs shifted to the right have these effects: (i) reduced BP, (ii) decreased organ damage and/or (iii) there is clinical evidence of cardiovascular benefits. Drugs on the left of the figure indicate that one or more of these conditions were met: (i) does not have clinical evidence in hypertension, only experimental; (ii) it works in one hypertensive model and others had no effect and/or (iii) it is toxic to the cardiovascular system. The centre position indicates intermediary effects, with risks and benefits to hypertension. Overall, this figure correlates the risk–benefit ratio to treat hypertension. Anti‐IL‐17AR, IL 17A receptor antibody; BAS, basiliximab; MMF, mycophenolate mofetil; Tac, tacrolimus.