The role of endogenous interleukin-1 in stress-induced adrenal activation and adrenalectomy-induced adrenocorticotropic hormone hypersecretion.
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.
Goshen
I
I
Department of Psychology, The Hebrew University of Jerusalem, Jerusalem 91905, Israel.
Yirmiya
R
R
Iverfeldt
K
K
Weidenfeld
J
J
D000311:Adrenal Glands / Q000503:physiopathology*; D000315:Adrenalectomy; D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000375:Aging / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000254:growth & development; D003345:Corticosterone / Q000378:metabolism; D007375:Interleukin-1 / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011184:Postoperative Period; D017472:Receptors, Interleukin-1 / Q000172:deficiency; D015398:Signal Transduction / Q000502:physiology; D013312:Stress, Physiological / Q000503:physiopathology*
D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone