Blunted cortisol response after administration of corticotropin releasing hormone in endotoxemic dogs

To evaluate the effects of a standard inflammatory challenge on the dynamics of the hypothalamic-pituitary-adrenal (HPA) axis, we studied the effects of low-dose endotoxin (1.0 mu g/kg) on plasma adrenocorticotropic hormone (ACTH) and cortisol concentrations in a saline-controlled study in five awake dogs. Four hours after endotoxin or saline challenge human corticotrophin-releasing hormone (hCRH; 1.0 mu g/kg) was administered. Plasma ACTH and cortisol levels increased considerably in response to endotoxin, from 13+/-1 ng/l to 360+/-8.5 ng/l (p<0.01) and from 60+/-20 nmol/l to 710+/-80 nmol/l (p<0.01). Despite a considerable difference in ACTH and cortisol levels prior to CRH administration between both studies (p<0.01), the absolute increase in ACTH levels induced by hCRH was not different (231+/-43 ng/l vs 238+/-45 ng/l, control vs endotoxin). Plasma cortisol levels increased significantly in the control study (from 40+/-10 nmol/l to 330+/-40 nmol/l, p<0.01), whereas they did not change in the endotoxin study after hCRH administration (from 710+/-80 nmol/l to 730+/-70 nmol/l, ns). We conclude that the HPA-axis reacts initially to endotoxin in such a way that cortisol, but not ACTH, secretion is maximized. Therefore, a blunted cortisol response to CRH testing is part of the initial response to infection. (C) 1997, Editrice Kurtis.