Heart, Spleen, Brain

Abstract

E volutionary pressure produced 2 master regulators of physiological homeosta-sis: the nervous system and the immune system. The nervous system evolved to integrate physiological functions and control changes in homeostasis. Neu-ral signals establish reflex responses, perceive disturbances in the environment (in-ternal or external), and elicit activation of the afferent arc (ie, the neural circuit that transfers information from the periphery to the brain). The central nervous system integrates these messages and transduces an output signal through the efferent arc, which conveys the reflex response to the innervated system, which can modulate organ functions. The immune system is the body's defense against infection or sterile tissue injury ; when challenged by disturbances deriving from the exterior or interior milieu, it has the task of balancing inflammation in the affected organ. Whatever the threat to homeostasis, immunity orchestrates complex responses comprising an initial defense phase that typically entails tissue destruction followed by a reparative phase. However, in some conditions, resolution of the destructive phase fails, and excessive inflammation can trigger ongoing damage and aberrant immune responses. Although interaction between these 2 evolutionarily highly conserved systems is long recognized, characterized even in ancient species, investigation into patho-physiological mechanisms regulating their reciprocal cross-talk has been the object of pathbreaking immunology and neuroscience research only in recent decades. This is particularly the case of cardiovascular biology. NEURAL SIGNALS CONTROLLING IMMUNE RESPONSES In 2000, almost 20 years ago, Kevin Tracey discovered that a neural reflex passing through the vagus nerve modulates the systemic immune response to pathogenic invasion , a phenomenon thereafter referred as the cholinergic antiinflammatory pathway. 1 After further investigation, it became clear that this vagal reflex involved nico-tinic acetylcholine receptors, specifically the α 7 subunit (α7nAChR). This observation, showing for the first time the existence of neural-immune interactions, paved the way for many subsequent preclinical investigations that broadened our understanding of neural regulation of immunity. 2 Research seeking to translate this concept into a therapeutic approach based on neuromodulating immune responses soon became a rapidly evolving field exploring the possibility to treat seriously debilitating conditions characterized by immune abnormalities and chronic inflammation.