Brain-Splenic Immune System Interactions in Hypertension: Cellular and Molecular Mechanisms

Abstract

Hypertension represents a major worldwide cause of death and disability, and it is becoming increasingly clear that available therapies are not sufficient to reduce the risk of major cardiovascular events. Various mechanisms contribute to blood pressure increase: neurohormonal activation, autonomic nervous system imbalance, and immune activation. Of note, the brain is an important regulator of blood pressure levels; it recognizes the peripheral perturbation and organizes a reflex response by modulating immune system and hormonal release to attempt at restoring the homeostasis. The connection between the brain and peripheral organs is mediated by the autonomic nervous system, which also modulates immune and inflammatory responses. Interestingly, an increased autonomic nervous system activity has been correlated with an altered immune response in cardiovascular diseases. The spleen is the largest immune organ exerting a potent influence on the cardiovascular system during disease and is characterized by a dense noradrenergic innervation. Taken together, these aspects led to hypothesize a key role of neuroimmune mechanisms in the onset and progression of hypertension. This review discusses how the nervous and splenic immune systems interact and how the mechanisms underlying the neuroimmune cross talk influence the disease progression.

Immune Mechanisms in Hypertension

“…The brain-splenic immune axis has been reviewed recently in depth. 125 It should be noted that most of the studies of splenic innervation in hypertension have been performed in mice, in which the spleen represents a predominant lymphoid organ. Beta 2 adrenergic receptors in the bone marrow likely play an important role in homing and maintenance of memory T cells in hypertension, and their ability to be reactivated upon a second hypertensive stimulus.…”