The response of the pituitaryadrenal axis following the administration of a bacterial pyrogen has been investigated in normal subjects at different times in the 24 hr. Bacterial pyrogen was injected at 4 am, 9 am, 5 pm and 11 pm. The increase of plasma cortisol after pyrogen injection was greatest at 11 pm and least at 9 am. There was a highly significant negative correlation between the plasma cortisol level before pyrogen injection and the maximal increase of plasma cortisol after pyrogen injection. Plasma ACTH was assayed in the same subjects who received pyrogen at 9 am and 11 pm. The increment of plasma ACTH was found in the subjects who received pyrogen at 11 pm, but in none of the subjects at 9 am. Therefore, it is apparent that there is a circadian rhythm in the pituitary response after pyrogen injection and pyrogen acts through the pituitary on the adrenal cortex. There was no correlation between the febrile response and the cortisol response after pyrogen injection.
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Takebe et al. (1966) studied this question.