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.
Prospective, controlled experiment.
Basic science laboratory.
Sprague-Dawley male rats 300–450 g.
Indwelling arterial catheters and CLP with either an 18-(CLP18) or a 21-gauge needle or sham surgery.
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).
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.
From the Departments of Surgery (DEC, WCC, TMS) and Physiology (DEC), Program in Trauma, R. Adams Cowley Shock Trauma Center, University of Maryland School of Medicine, Baltimore, MD.
Supported, in part, by National Institute of General Medical Sciences Grant GM 063050 from the National Institutes of Health, Bethesda, MD.
The authors have disclosed that they hold no financial interests related to the conduct or results of this research.