Atrial natriuretic peptide: an old hormone or a new cytokine?

Atrial natriuretic peptide (ANP) a cardiovascular hormone mainly secreted by heart atria in response to stretching forces induces potent diuretic, natriuretic and vasorelaxant effects and plays a major role in the homeostasis of blood pressure as well as of water and salt balance. The hormone can also act as autocrine/paracrine factor and modulate several immune functions as well as cytoprotective effects. ANP contributes to innate immunity being able to: (i) stimulate the host defense against extracellular microbes by phagocytosis and Reactive Oxygen Species (ROS) release; (ii) inhibit the synthesis and release of proinflammatory markers such as TNF-α, IL-1, MCP-1, nitric oxide (NO), cyclooxygenase-2 (COX-2); (iii) inhibit the expression of adhesion molecules such as ICAM-1 and E-selectin. ANP can also affect the adaptive immunity being able to: (i) reduce the number of CD4(+) CD8(+) lymphocytes as well as to increase the CD4(-) CD8(-) cells; (ii) stimulate the differentiation of naïve CD4(+) cells toward the Th2 and/or Th17 phenotype. The hormone shows protective effects during: (i) ventricular hypertrophy and myocardial injury; (ii) atherosclerosis and hypertension by the induction of antiproliferative effects; (iii) oxidative stress counteracting the dangerous effects of ROS; (iv) growth of tumors cells by the induction of apoptosis or necrosis. Since not much is known about of the role of ANP locally produced and released by non-cardiac cells, this review outlines the contribution of ANP in different aspect of innate as well as adaptive immunity also with respect to the excessive cell growth in physiological and/or pathological conditions.