Immune Cells and Cytokine Circuits: Toward a Working Model for Understanding Direct Immune-to-Adrenal Communication Pathways

Although the adrenal glands were anatomically identified nearly 450 yr ago, their vital role in physiology was not established until considerably later (1). We now know that the adrenal glands, despite their miniature size, play an indispensable role in homeostatic functions ranging from regulation of ion balances to being a final site of integration for the stress response. When considering the many masters that oversee adrenal output, most people can readily recite three principle sources of adrenal regulation: 1) the kidney, which regulates mineralocorticoid secretion through the renin-angiotensin system; 2) the pituitary gland, which regulates glucocorticoid secretion via ACTH; and 3) the splanchnic nerve, which regulates blood flow to the adrenal and innervates the medulla, thereby regulating secretion of catecholamines and other stress-responsive factors into systemic circulation.