Table 2:

The knowns and unknowns of the role of the immune system in hypertension.

Knowns	Unknowns
TLR-4 gene–deficient mouse models have exhibited less blood pressure rise in reaction to angiotensin II or L-NAME infusions. Blocking TLR-9 is associated with a decrease in angiotensin II–induced hypertension.	Although early studies suggest a possible role in the pathophysiology and identification as a potential therapeutic target by injection of anti-CD20 antibodies, the significance of B-lymphocytes has largely been uninvestigated in research on hypertension. Further research on the function of B-lymphocytes in the pathophysiology of hypertension is highly necessary.
Numerous pre-clinical investigations using angiotensin II- or aldosterone-induced hypertension models have shown increased circulating monocytes. Rats that develop hypertension spontaneously or in salt-sensitive or deoxycorticosterone acetate–induced hypertension models have shown a similar trend.	There is little information on how eosinophils and basophils contribute to the etiology of hypertension. Observational studies have suggested a possible connection between coronary artery disease or pulmonary artery hypertension and a higher peripheral eosinophil count, although the precise relationship has not yet been proven.
Hs-CRP, IL-6 and elevated CRP were all substantially associated with an increased risk of developing hypertension. IL-1β, however, was not linked to a serious risk.	Although studies using on animal models clearly show the major involvement of renal inflammation in the pathogenesis of hypertension, it is not apparent whether renal inflammation is the triggering event that results in clinical hypertension or only a contributing factor to the onset of hypertension.
In people with primary hypertension, mRNA and protein of TGF-β1 are found to be overexpressed.	Further research is necessary to fully understand the impact of TNF- and its inhibition on blood pressure readings because there are conflicting results in the literature.
High blood pressure was hypothesized to enhance TNF and oxidative stress significantly. According to a different study, patients with hypertension had considerably higher TNF levels in their blood and urine than healthy controls.	Further studies are needed to understand how dietary salt intake and immune response are linked to hypertension and cardiovascular illnesses.
Immune system cells infiltrate the kidneys of spontaneously hypertensive rats before clinical hypertension manifests itself. Furthermore, there is a strong correlation between the level of SBP measurements and immune cell infiltration.
A preclinical investigation using a transgenic mouse model with monocyte/macrophage depletion revealed a decrease in superoxide radical generation, a reduction in angiotensin II–induced hypertension and a reduction in vascular dysfunction.
The release of pro-fibrotic cytokines like TGF and the remodeling of the extracellular matrix by matrix metalloproteinases, which cause vascular stiffness, are two crucial pathophysiological roles of macrophages in vascular inflammation.
T-regulatory cells could prevent vascular inflammation. These cells seem to prevent angiotensin II- or aldosterone-induced ROS production and monocyte/macrophage infiltration of the vascular wall.
T-regulatory cell administration as a single dose or once weekly dose improves cardiac hypertrophy, endothelial vasodilatation, the production of ROS and pro-inflammatory signals, but has no effect on blood pressure readings. In contrast, administering T-regulatory cells at sustained high doses improves blood pressure.
High dietary sodium intake not only causes hemodynamic alterations but also modulates the immune system by immune cell activation, vascular endothelial dysfunction and cytokine secretion, eventually leading inflammation and hypertension.

SBP: systolic blood pressure.