Dimitris A. Papanicolaou, MD; Ronald L. Wilder, MD, PhD; Stavros C. Manolagas, MD, PhD; George P. Chrousos, MD
Interleukin-6, an inflammatory cytokine, is characterized by pleiotropy and redundancy of action. Apart from its hematologic, immune, and hepatic effects, it has many endocrine and metabolic actions. Specifically, it is a potent stimulator of the hypothalamic-pituitary-adrenal axis and is under the tonic negative control of glucocorticoids. It acutely stimulates the secretion of growth hormone, inhibits thyroid-stimulating hormone secretion, and decreases serum lipid concentrations. Furthermore, it is secreted during stress and is positively controlled by catecholamines. Administration of interleukin-6 results in fever, anorexia, and fatigue. Elevated levels of circulating interleukin-6 have been seen in the steroid withdrawal syndrome and in the severe inflammatory, infectious, and traumatic states potentially associated with the inappropriate secretion of vasopressin. Levels of circulating interleukin-6 are also elevated in several inflammatory diseases, such as rheumatoid arthritis. Interleukin-6 is negatively controlled by estrogens and androgens, and it plays a central role in the pathogenesis of the osteoporosis seen in conditions characterized by increased bone resorption, such as sex-steroid deficiency and hyperparathyroidism. Overproduction of interleukin-6 may contribute to illness during aging and chronic stress. Finally, administration of recombinant human interleukin-6 may serve as a stimulation test for the integrity of the hypothalamic-pituitary-adrenal axis.
Papanicolaou DA, Wilder RL, Manolagas SC, et al. The Pathophysiologic Roles of Interleukin-6 in Human Disease. Ann Intern Med. 1998;128:127–137. doi: 10.7326/0003-4819-128-2-199801150-00009
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Published: Ann Intern Med. 1998;128(2):127-137.
Endocrine and Metabolism, Fluid and Electrolyte Disorders, Lupus Erythematosus, Metabolic Bone Disorders, Nephrology.
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