Cecal ligation and puncture in rats interrupts the circadian rhythms of corticosterone and adrenocortical responsiveness to adrenocorticotrophic hormone.
OBJECTIVE
To determine the altered patterns of pituitary-adrenal activity and impaired adrenocortical sensitivity to adrenocorticotrophic hormone (ACTH) in the cecal ligation and puncture (CLP) model of sepsis.


METHODS
Prospective, controlled experiment.


METHODS
Basic science laboratory.


METHODS
Sprague-Dawley male rats 300-450 g.


METHODS
Indwelling arterial catheters and CLP with either an 18-(CLP18) or a 21-gauge needle or sham surgery.


RESULTS
Plasma ACTH and corticosterone recovered most rapidly after sham surgery and least rapidly after CLP18. From postoperative day 4 am through day 7, a robust diurnal rhythm of corticosterone (p < .001) with a modest rhythm of ACTH (p < .01) occurred only in sham rats, and the slope of the regression between plasma corticosterone and ACTH increased from am to pm after sham surgery (p < .05) but not after CLP. Corticosterone in response to intravascular ACTH (3, 10, and 250 ng/kg) 2 hrs after dexamethasone (0.25 mg/kg) only showed an am to pm difference after sham surgery. The pm sham responses to all doses of ACTH were greater (p < .01) than the respective am sham responses that were not different from the respective am or pm responses after CLP. Corticosterone after 10 ng/kg ACTH in the pm decreased as plasma macrophage migration inhibitory factor and IL-6 increased after CLP (r = -.691 and r = -.813, respectively; p < .02 in each case).


CONCLUSIONS
The adrenocortical sensitivity to ACTH in the pm after CLP is suppressed progressively with the intensity of inflammation. This suppression appears to be a major factor in the interruption of circadian patterns of hormonal secretion in sepsis.
Carlson
Drew E
DE
Department of Surgery, Program in Trauma, R. Adams Cowley Shock Trauma Center, University of Maryland School of Medicine, Baltimore, USA.
Chiu
William C
WC
Scalea
Thomas M
TM
D000302:Adrenal Cortex / Q000503:physiopathology*; D000324:Adrenocorticotropic Hormone / Q000502:physiology*; D000818:Animals; D002432:Cecum / Q000601:surgery*; D002940:Circadian Rhythm; D003345:Corticosterone / Q000502:physiology*; D008026:Ligation; D008297:Male; D010913:Pituitary-Adrenal System / Q000503:physiopathology*; D011677:Punctures; D051381:Rats; D017207:Rats, Sprague-Dawley
D000324:Adrenocorticotropic Hormone; D003345:Corticosterone