The pathophysiologic roles of interleukin-6 in human disease

Ann Intern Med. 1998 Jan 15;128(2):127-37. doi: 10.7326/0003-4819-128-2-199801150-00009.


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.

Publication types

  • Consensus Development Conference
  • Consensus Development Conference, NIH
  • Review

MeSH terms

  • Aging / physiology
  • Autoimmune Diseases / physiopathology
  • Bone Diseases / physiopathology
  • Endocrine System / physiology
  • Female
  • Humans
  • Immune System / physiology
  • Inflammation / physiopathology
  • Interleukins / genetics
  • Interleukins / metabolism
  • Interleukins / physiology*
  • Male
  • Osteoporosis / physiopathology
  • United States


  • Interleukins