Cytokine-induced activation of the neuroendocrine stress axis persists in endotoxin-tolerant mice.
Chronic administration of lipopolysaccharide (LPS) to mice markedly reduced activation of the neuroendocrine stress axis elicited by an acute challenge dose of LPS. LPS-induced elevation in norepinephrine turnover in the hypothalamus showed complete tolerance whereas elevation of plasma corticosterone showed only partial tolerance. Challenge-induced increased turnover of dopamine in hypothalamus persisted in LPS-tolerant animals. Neuroendocrine activation persisted following acute challenge with interleukin-1 and tumor necrosis factor following chronic LPS exposure.
Mefford
I N
IN
Section of Clinical Pharmacology, National Institute of Mental Health, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892.
Masters
C F
CF
Heyes
M P
MP
Eskay
R L
RL
D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism; D003345:Corticosterone / Q000378:metabolism; D016207:Cytokines / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D004361:Drug Tolerance; D004731:Endotoxins / Q000633:toxicity*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D007375:Interleukin-1 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000633:toxicity; D008264:Macrophages / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009490:Neurosecretory Systems / Q000187:drug effects / Q000502:physiology*; D009638:Norepinephrine / Q000378:metabolism; D013312:Stress, Physiological / Q000503:physiopathology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D015306:Biogenic Monoamines; D016207:Cytokines; D004731:Endotoxins; D007375:Interleukin-1; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D004298:Dopamine; D003345:Corticosterone; D009638:Norepinephrine