The hypothalamic pituitary adrenal axis in sepsis.

At the beginning of the 20th century, observations of apoplectic adrenal glands in fatal meningococcemia underlined their key role in host defence against infection. Thirty years later, cortisone was discovered and rapidly proven to have numerous and diversified physiological functions in the host response to stress. Corticosteroids were introduced in the treatment of severe infection as early as in the 1940s. Several 'negative' randomized controlled trials of high-dose of glucocorticoids given for a short period of time in the early course of severe sepsis or acute respiratory distress syndrome raised serious doubts as to the benefit of this treatment. Recently, a link between septic shock and adrenal insufficiency, or systemic inflammation-induced glucocorticoid receptor resistance has been established. This finding prompted renewed interest in a replacement therapy with low doses of corticosteroids during longer periods. We will review the key role of the hypothalamic-pituitary-adrenal axis in the host response to stress.