The pathophysiologic roles of interleukin-6 in human disease.
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
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Wilder
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Manolagas
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Chrousos
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D000375:Aging / Q000502:physiology; D001327:Autoimmune Diseases / Q000503:physiopathology; D001847:Bone Diseases / Q000503:physiopathology; D004703:Endocrine System / Q000502:physiology; D005260:Female; D006801:Humans; D007107:Immune System / Q000502:physiology; D007249:Inflammation / Q000503:physiopathology; D007378:Interleukins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008297:Male; D010024:Osteoporosis / Q000503:physiopathology; D014481:United States
D007378:Interleukins