THE ROLE OF THE HYPOTHALAMIC-PITUITARY-ADRENOCORTICAL SYSTEM DURING INFLAMMATORY CONDITIONS

Infections and injury are often accompanied by the production of large quantities of proinflammatory mediators such as cytokines and eicosan oids. These substances have been shown to efficiently activate the hyp othalamic-pituitary-adrenocortical (HPA) system. The glucocorticoid ho rmones secreted from the adrenal cortex seem to be crucial for surviva l because they have an inhibitory influence on inflammatory processes, which, if uncontrolled, may become toxic for the host. Furthermore, t hese steroid hormones are known to support thermogenesis by inducing o r repressing key enzymes of carbohydrate, lipid, and protein metabolis m, and thus may also facilitate energy mobilization during fever, whic h usually accompanies infectious diseases. Finally, a number of studie s suggest that glucocorticoids attenuate debilitating symptoms of infl ammatory mediators, such as sleepiness, loss of appetite, and suppress ion of reproductive functions. One can assume that glucocorticoids exe rt similar behavioral effects during inflammatory conditions, which ar e seen in infectious diseases. Corticotropin-releasing hormone (CRH), the major hypothalamic component of the HPA system, is a putative medi ator of the central effects of cytokines and autacoids because it inhi bits growth, reproduction, and food intake. In contrast, CRH decreases sleep duration. Vasopressin, another hypothalamic peptide of the HPA system, counteracts fever and sickness behavior and is thought to supp ort recovery from inflammatory diseases. Apparently, a well-balanced, concerted action of proinflammatory mediators, glucocorticoids, and hy pothalamic peptide hormones provides not only an efficient principle f or combating microorganisms and support of tissue repair but also for self-protection of the host during the stress of inflammation. Therefo re, an impairment of the HPA system under inflammatory conditions ofte n has severe pathological consequences, for example, in patients suffe ring from Addison's disease and arthritis.