DIURNAL-VARIATIONS IN THE HUMAN REST RESPONSE TO ENDOTOXIN

To investigate diurnal variations in the host response to endotoxin, S almonella abortus equi endotoxin (0.8 ng/kg) was given intravenously t o healthy men in a placebo-controlled design at 0900 or 1900 h. The ti me courses of rectal temperature and the plasma levels of tumor necros is factor-alpha (TNF-alpha), interleukin-6 (IL-6), adrenocorticotropic hormone (ACTH), and cortisol were monitored for 11 h following the in jections. The time of day did not affect the endotoxin-induced increas e in plasma TNF-alpha or IL-6, However, subjects who received endotoxi n in the evening, when endogenous glucocorticoid levels were low, show ed about twice the increases in rectal temperature and plasma ACTH and cortisol levels as those who received endotoxin in the morning, when endogenous glucocorticoid levels were high, These results demonstrate diurnal variations in the human susceptibility to endotoxin that may b e due to a suppression of the biologic effects of TNF-alpha and IL-S b y endogenous glucocorticoids.