Neuro-hormonal host defence in endotoxin shock.
The sensitivity (LD100) of mice to lipopolysaccharide (LPS) endotoxin and to its toxic moiety, lipid A (LA), increased 500-fold after adrenalectomy (ADX). Inhibition of glucocorticoid synthesis in intact mice by metyrapone had a similar, though less dramatic, sensitizing effect to LPS. In ADX mice, the serum level of tumor necrosis factor-alpha (TNF) was 40-60 times higher than that in controls at 2 h after LPS/LA treatment. In intact mice the serum corticosterone level fell 1 h after lipid A injection to below detectable levels, which was followed by a brisk increase reaching the peak level of 48-50 micrograms/100 ml at 2 h. Both TNF production and the lethal effect of PLS/LA could be inhibited in ADX mice by glucocorticoid treatment. Plasma prolactin was increased significantly 1 h after endotoxin administration in both intact and ADX animals.
Ramachandra
R N
RN
Department of Immunology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
Sehon
A H
AH
Berczi
I
I
D000315:Adrenalectomy; D000818:Animals; D003345:Corticosterone / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology / Q000627:therapeutic use; D004198:Disease Susceptibility / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D005260:Female; D008050:Lipid A / Q000633:toxicity; D008070:Lipopolysaccharides / Q000633:toxicity; D008797:Metyrapone / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C / Q000276:immunology / Q000502:physiology; D010913:Pituitary-Adrenal System / Q000503:physiopathology*; D011388:Prolactin / Q000378:metabolism; D012772:Shock, Septic / Q000276:immunology / Q000503:physiopathology* / Q000517:prevention & control; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D008050:Lipid A; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D011388:Prolactin; D003345:Corticosterone; D008797:Metyrapone