Both inflammatory and endocrine mediators stimulate host responses to sepsis.

Host responses to sepsis and trauma are complex and their mediators are not well understood. To examine the roles of "endocrine" and "inflammatory" mediators, we studied healthy volunteers in four experimental groups: continuous 72-hour infusion of normal saline; continuous 72-hour infusion of hydrocortisone, glucagon, and epinephrine; daily intramuscular injection of the inflammatory agent etiocholanolone; and combined etiocholanolone injection--hormone infusion. In this model hypermetabolism, hyperglycemia, hyper-insulinemia, insulin resistance, negative nitrogen balance, and accelerated protein flux were mediated predominantly by infusion of the counterregulatory hormones. Etiocholanolone injection resulted in fever, acute-phase--protein synthesis, and hypoferremia. Leukocyte, temperature, and C-reactive--protein responses reflected major interactions between these stimuli. Both inflammatory and endocrine mediators are necessary for the complete manifestation of host responses to critical illness.