Interleukin-6 and the interleukin-6 receptor in the human adrenal gland: expression and effects on steroidogenesis

J Clin Endocrinol Metab. 1997 Jul;82(7):2343-9. doi: 10.1210/jcem.82.7.4072.


Interleukin (IL)-6 is a potent activator of the human hypothalamicpituitary-adrenal axis. After chronic administration of IL-6 in humans, there is a substantial elevation of cortisol, whereas ACTH levels are blunted. Thus, we investigated whether IL-6 and/or the IL-6 receptor (IL-6R) are expressed in the human adrenal gland and whether IL-6 could cause the release of steroid hormones by a direct action on adrenal cells in primary culture. The expression of IL-6 and IL-6R was investigated with RT-PCR and immunohistochemistry, and the effects on human adrenal steroidogenesis were tested with IL-6 in vitro. To avoid effects mediated by macrophages, we depleted adrenal primary cultures from macrophages using specific mouse antihuman CD68 and sheep antimouse IgG conjugated magnetic beads. The results showed that 1): IL-6 and IL-6R are expressed in adrenal cell cultures, including all cell types and those depleted of macrophages; 2) IL-6R is mainly expressed in the zona reticularis and the inner zona fasciculata; positive signals from the zona glomerulosa and the medulla occurred in single cells; and 3) IL-6 regulates adrenal synthesis of mineralocorticoids, glucocorticoids, and androgens in vitro, dependent on time and dose, in the absence of macrophages. After 24 h, aldosterone secretion increased to 172 +/- 28% SEM, cortisol to 177 +/- 27% SEM, and dehydroepiandrosterone to 153 +/- 20% SEM of basal secretion. These findings, in combination with previous investigations, suggest that IL-6 exerts its acute action via the hypothalamus and the pituitary. In the adrenal gland, however, IL-6 seems to be a long-term regulator of stress response, integrating the responses of all cortical zones to stimuli from the immune and endocrine system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Glands / drug effects
  • Adrenal Glands / metabolism*
  • Adrenocorticotropic Hormone / pharmacology
  • Aged
  • Aldosterone / metabolism
  • Antigens, CD / metabolism*
  • Cells, Cultured
  • Dehydroepiandrosterone / metabolism
  • Humans
  • Hydrocortisone / metabolism
  • Immunohistochemistry
  • Interleukin-6 / metabolism*
  • Interleukin-6 / pharmacology
  • Middle Aged
  • RNA, Messenger / metabolism
  • Receptors, Interleukin / metabolism*
  • Receptors, Interleukin-6
  • Time Factors


  • Antigens, CD
  • Interleukin-6
  • RNA, Messenger
  • Receptors, Interleukin
  • Receptors, Interleukin-6
  • Dehydroepiandrosterone
  • Aldosterone
  • Adrenocorticotropic Hormone
  • Hydrocortisone