Immunomodulation in septic shock: Hydrocortisone differentially regulates cytokine responses

Cortisol is known to be an immunomodulatory hormone that exerts suppressive and permissive effects on the immune response. Little is known regarding t he evolution of the cytokine response in human septic shock in the presence of hypercortisolemia induced by infusion of stress doses of hydrocortisone . Twenty-four consecutive patients with high-output circulatory failure (ca rdiac index, >4 liters/min per m(2)) who met the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference Committee criteria for septic shock were enrolled in a prospective, double-blind stu dy. The severity of illness at the time of enrollment was graded using the Acute Physiology and Chronic Health Evaluation II system, and the evolution of sepsis-induced organ dysfunction syndrome was assessed using Sepsis-Rel ated Organ Failure Assessment scores. After randomization, hyper cortisolem ia was induced in 12 patients by infusion of 100 mg of hydrocortisone, foll owed by continuous infusion of 0.18 mg/kg per h. Levels of the circulating cytokines tumor necrosis factor alpha (TNF), interleukin 6 (IL-6), IL-8, an d IL-10 were serially measured at prospectively defined time points during the first 5 d after randomization. The infusion of hydrocortisone was assoc iated with significant reductions in serum IL-6 and IL-8 levels and with ea rlier resolution of the sepsis-induced organ dysfunction syndrome. IL-6 lev els started to differ between the groups on day 5. The TNF and IL-10 respon ses were not altered by hydrocortisone infusion. Hydrocortisone infusion in septic shock differentially regulated the cytokine responses. IL-6 and IL- 8 levels decreased significantly and IL-6 levels differed between the group s, whereas TNF and IL-10 levels were not affected by hydrocortisone. Stress doses of hydrocortisone may be a valuable immunomodulatory therapy for sep tic shock.