Immunosuppression in Patients Who Die of Sepsis and Multiple Organ Failure

Abstract

Sepsis is responsible for more than 225 000 deaths annually in the United States.¹ Developing new therapies for sepsis has been particularly challenging, with more than 25 unsuccessful drug trials.^2-6 Characterized by an initial intense inflammatory response or “cytokine storm,” patients with sepsis may present with fever, shock, altered mental status, and organ dysfunction.^5-8 Numerous investigative agents have been directed at down-modulating this initial phase. Improved clinical management algorithms have led to survival of the majority of patients in this early period.^9-11 Quiz Ref ID However, those who survive early sepsis often develop nosocomial infections with organisms not typically pathogenic in immunocompetent hosts and have reactivation of latent viruses.^9,12,13 These observations have led to the controversial hypothesis that the early hyperinflammatory state evolves to a subsequent hypoinflammatory state with significant immunosuppression.^14-19 Although animal studies demonstrate progression to an immunosuppressive phase, epidemiologic studies in clinical sepsis are lacking.^14-19 The purpose of this investigation was to assess evidence of immunosuppression in sepsis and to determine mechanisms that might be responsible for the presumed impaired immunity. Cells from spleen and lung were studied to compare and contrast the functional status and phenotype of cells from a lymphoid organ and a peripheral organ that is a frequent site of nosocomial infection.