THE PATHOPHYSIOLOGIC ROLES OF INTERLEUKIN-6 IN HUMAN-DISEASE

Interleukin-6, an inflammatory cytokine, is characterized by pleiotrop y and redundancy of action. Apart from its hematologic, immune, and he patic effects, it has many endocrine and metabolic actions. Specifical ly, it is a potent stimulator of the hypothalamic-pituitary-adrenal ax is and is under the tonic negative control of glucocorticoids. It acut ely stimulates the secretion of growth hormone, inhibits thyroid-stimu lating hormone secretion, and decreases serum lipid concentrations. Fu rthermore, it is secreted during stress and is positively controlled b y catecholamines. Administration of interleukin-6 results in fever, an orexia, and fatigue. Elevated levels of circulating interleukin-6 have been seen in the steroid withdrawal syndrome and in the severe inflam matory, infectious, and traumatic states potentially associated with t he inappropriate secretion of vasopressin. Levels of circulating inter leukin-6 are also elevated in several inflammatory diseases, such as r heumatoid arthritis. Interleukin-6 is negatively controlled by estroge ns and androgens, and it plays a central role in the pathogenesis of t he osteoporosis seen in conditions characterized by increased bone res orption, such as sex-steroid deficiency and hyperparathyroidism. Overp roduction of interleukin-6 may contribute to illness during aging and chronic stress. Finally, administration of recombinant human interleuk in-6 may serve as a stimulation test for the integrity of the hypothal amic-pituitary-adrenal axis.