The Pathophysiologic Roles of Interleukin-6 in Human Disease

  1. Dimitris A. Papanicolaou, MD;
  2. Ronald L. Wilder, MD, PhD;
  3. Stavros C. Manolagas, MD, PhD; and
  4. George P. Chrousos, MD
  1. An edited summary of a Clinical Staff Conference held on 13 March 1996 at the National Institutes of Health, Bethesda, Maryland. Authors who wish to cite a section of the conference and specifically indicate its author may use this example for the form of the reference: Wilder RL. Interleukin-6 in autoimmune and inflammatory diseases, pp 130-132. In: Papanicolaou DA, moderator. The pathophysiologic roles of interleukin-6 in human disease. Ann Intern Med. 1998; 128:127-137. For definitions of terms used in the text, see Glossary at end of text. Requests for Reprints: Dimitris A. Papanicolaou, MD, Developmental Endocrinology Branch, National Institute of Child Health and Human Development, Building 10, Room 10N262, 10 Center Drive MSC 1862, Bethesda, MD 20892-1862 Current Author Addresses: Dr. Papanicolaou: Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Building 10, Room 10N262, 10 Center Drive MSC 1862, Bethesda, MD 20892-1862.

    Abstract

    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.

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    1. Ann Intern Med January 15, 1998 vol. 128 no. 2 127-137
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