The role of endogenous interleukin-1 in stress-induced adrenal activation and adrenalectomy-induced adrenocorticotropic hormone hypersecretion

Endocrinology. 2003 Oct;144(10):4453-8. doi: 10.1210/en.2003-0338. Epub 2003 Jul 10.


To examine the role of IL-1 in the regulation of the hypothalamo-pituitary-adrenal (HPA) axis, mice with knockout of the IL-1 receptor type I (IL-1rKO) were exposed to psychological and metabolic stressors. When exposed to mild stressors (auditory stress or a low dose of 2-deoxyglucose), IL-1rKO mice displayed a significantly diminished corticosterone secretion, compared with wild-type (WT) controls. In response to more severe stressors (60-min restraint or a high dose of 2-deoxyglucose), both groups exhibited a similar increase in corticosterone secretion. To examine the role of IL-1 in HPA axis feedback regulation, serum ACTH levels were measured after adrenalectomy (ADX) in IL-1rKO mice and in mice with transgenic overexpression of IL-1 receptor antagonist within the brain (IL-1raTG). As expected, WT controls exhibited ADX-induced ACTH hypersecretion, whereas IL-1rKO and IL-1raTG mice showed no increase in ACTH levels, suggesting that brain IL-1 has a critical role in ADX-associated ACTH hypersecretion. Similarly, WT mice that were chronically exposed to IL-1ra in utero displayed a diminished ADX-induced ACTH hypersecretion, compared with vehicle-treated controls, suggesting a developmental role of IL-1 in HPA axis regulation. In conclusion, our results suggest that endogenous IL-1 plays a critical role in HPA axis activation after stress and ADX.

MeSH terms

  • Adrenal Glands / physiopathology*
  • Adrenalectomy*
  • Adrenocorticotropic Hormone / metabolism*
  • Aging / metabolism
  • Animals
  • Brain / growth & development
  • Corticosterone / metabolism
  • Interleukin-1 / physiology*
  • Male
  • Mice
  • Mice, Knockout
  • Postoperative Period
  • Receptors, Interleukin-1 / deficiency
  • Signal Transduction / physiology
  • Stress, Physiological / physiopathology*


  • Interleukin-1
  • Receptors, Interleukin-1
  • Adrenocorticotropic Hormone
  • Corticosterone