Glucocorticoid receptor effects on the immune system and infl ammation

Abstract

Thomas Addison’s discovery in the mid-1800s that the adrenal cortex was essential for survival preceded by nearly a century the demonstration that this gland produced at least two distinct hormones, each essential for normal life. How glucocorticoids sustained life remained a mystery for decades. In 1949 glucocorticoids were found to have powerful anti-infl ammatory activity, a discovery which led to their use as “miracle drugs” in many diseases 1. Since their introduction in 1948, they have become so important that some authors divide the history into BC and AC (before cortisol and after cortisol) 2. Today, glucocorticoids are among the most important drugs used in routine clinical practice because of their clinically important anti-infl ammatory and immunosuppressive effects. The list of indications for glucocorticoid treatment is long. Diseases in which glucocorticoid treatment plays a major role include common disorders such as asthma, nephrotic syndrome, rheumatoid arthritis, dermatological diseases, Crohn’s disease, systemic diseases, organ transplantation, and malignancies. However, serious adverse effects often accompany treatment. Many adverse effects are partly or mainly caused by glucocorticoid receptor transactivating effects. By contrast, anti-infl ammatory effects are mostly mediated by glucocorticoid receptor transrepression. The challenge is balancing desired therapeutic effects and adverse reactions. Recently, population based individual variability in cortisol sensitivity and its implications for health profi les and risk for disease is coming into focus