Glucocorticoids and natural killer cells: A suppressive relationship

glucocorticoid system’s canonical physiological stress response. They affect the immune system at the levels ofinflammation and adaptive and innate immunity. These effects are the basis for therapeutic use of glucocorticoids.Innate immunity is the body’s first line of defense against disease conditions. It is relatively nonspecificand, among its mediators, natural killer (NK) cells link innate and acquired immunity. NK cell numbers arealtered in patients with auto immune diseases, and research suggests that interactions between glucocorticoidsand natural killer cells are critical for successful glucocorticoid therapy. The aim of this review is to summarizethese interactions while highlighting the latest and most important developments in this field. Production andrelease in the blood of endogenous glucocorticoids are strictly regulated by the hypothalamus–pituitary adrenalaxis. A self-regulatory mechanism prevents excessive plasma levels of these hormones. However, exogenousstimuli such as stress, inflammation, infections, cancer, and autoimmune disease can trigger the hypothalamuspituitary-adrenal axis response and lead to excessive systemic release of glucocorticoids. Thus, stress stimuli,such as sleep deprivation, intense exercise, depression, viral infections, and cancer, can result in release ofglucocorticoids and associated immunosuppressant effects. Among these effects are decreases in the numbers andactivities of NK cells in inflammatory and autoimmune diseases (e.g., giant cell arteritis, polymyalgia rheumatica,and familial hypogammaglobulinemia).