Both cyclooxygenase-dependent and cyclooxygenase-independent pathways mediate the neuroendocrine response in humans

The neuroendocrine response that occurs after operation, trauma, or infection is essential for maintaining homeostasis within the host. Corticotropin-releasing hormone, (CRH), arginine vasopressin (AVP), and products of the cyclooxygenase pathway have been proposed as possible mediators of the pituitary-adrenal response. We studied the relationship between the induction of these mediators and the onset of the neuroendocrine response in healthy male volunteers receiving one of two standard provocative stimuli: (1) Escherichia coli endotoxin (4 ng/kg intravenously) and (2) hypoglycemia induced by insulin (0.15 units/kg intravenously). Additional subjects receiving these stimuli were pretreated with the cyclooxygenase inhibitor ibuprofen, 1600 mg orally. Serial measurements were made of circulating concentrations of CRH, AVP, adrenocorticotropic hormone, cortisol, and catecholamines. A sudden rise in circulating AVP (but not CRH) concentrations preceded the onset of all other responses after both stimuli. The prevention of this surge of AVP after endotoxin by ibuprofen was associated with blockade of the neuroendocrine response. These data demonstrate that two independent pathways are available for stimulation of the stress response. After both stimuli, peripheral AVP (but not CRH) levels may mirror alterations that occur within the central nervous system.