TY - JOUR
T1 - Activation of the hypothalamus-pituitary-adrenal axis by bacterial endotoxins
T2 - Routes and intermediate signals
AU - Tilders, Fred J.H.
AU - DeRuk, Roel H.
AU - Van Dam, Anne Marie
AU - Vincent, Valerie A.M.
AU - Schotanus, Karel
AU - Persoons, Jek H.A.
PY - 1994
Y1 - 1994
N2 - Peripheral administration of endotoxin induces brain-mediated responses, including activation of the hypothalamus-pituitary-adrenal (HPA) axis and changes in thermoregulation. This paper reviews the mechanisms by which endotoxin affects these responses. The effects on theroregulaton are complex and include macrophage-dependent hyperthermic and hypothermic responses. Low doses of endotoxin, given IP, activate peripheral macrophages to produce interleukin (IL)-1β, which enters the circulation and acts as a hormonal signal. IL-1 may pass fenestrated endothelium in the median eminence to stimulate corticotropin-releasing hormone (CRH) secretion from the CRH nerve-terminals. In addition, IL-1 may activate brain endothelial cells to produce IL-1, IL-6, prostaglandins, etc., and secrete these substances into the brain. By paracrine actions, these substances may affect neurons (e.g., CRH neurons) or act on microglial cells, which show IL-1-induced IL-1 production and therefore amplify and prolong the intracerebral IL-1 signal. In contrast, high doses of endotoxin given IV may directly stimulate endothelial cells to produce IL-1. IL-6, and prostaglandin-E2 (PGE2) and thereby activate the HPA axis in a macrophage-independent manner.
AB - Peripheral administration of endotoxin induces brain-mediated responses, including activation of the hypothalamus-pituitary-adrenal (HPA) axis and changes in thermoregulation. This paper reviews the mechanisms by which endotoxin affects these responses. The effects on theroregulaton are complex and include macrophage-dependent hyperthermic and hypothermic responses. Low doses of endotoxin, given IP, activate peripheral macrophages to produce interleukin (IL)-1β, which enters the circulation and acts as a hormonal signal. IL-1 may pass fenestrated endothelium in the median eminence to stimulate corticotropin-releasing hormone (CRH) secretion from the CRH nerve-terminals. In addition, IL-1 may activate brain endothelial cells to produce IL-1, IL-6, prostaglandins, etc., and secrete these substances into the brain. By paracrine actions, these substances may affect neurons (e.g., CRH neurons) or act on microglial cells, which show IL-1-induced IL-1 production and therefore amplify and prolong the intracerebral IL-1 signal. In contrast, high doses of endotoxin given IV may directly stimulate endothelial cells to produce IL-1. IL-6, and prostaglandin-E2 (PGE2) and thereby activate the HPA axis in a macrophage-independent manner.
UR - http://www.scopus.com/inward/record.url?scp=0028275378&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/0306-4530(94)90010-8
DO - https://doi.org/10.1016/0306-4530(94)90010-8
M3 - Review article
C2 - 8190840
SN - 0306-4530
VL - 19
SP - 209
EP - 232
JO - Psychoneuroendocrinology
JF - Psychoneuroendocrinology
IS - 2
ER -