Cytokine Storm and Sepsis-Induced Multiple Organ Dysfunction Syndrome

Abstract

The clinical features of primary hemophagocytic lymphohistiocytosis, rheumatological disease-associated macrophage activation syndrome, and hyperferritinemic sepsis-induced multiple organ failure overlap; however, the distinctive pathobiology that causes hyperinflammation in each condition requires different therapies. Primary hemophagocytic lymphohistiocytosis and rheumatologic macrophage activation syndrome are defined by five of eight clinical criteria. In the former normal natural killer cell numbers with absent cytolytic activity allow T-cell activation and proliferation-driven interferon-γ-induced hyperinflammation which is treated with etoposide, dexamethasone, and interferon-γ monoclonal antibody; whereas, in the latter natural killer cell numbers are normal and cytolytic activity is only decreased leading to interleukin-18 driven inflammation that is treated with corticosteroids and interleukin 1 receptor antagonist protein. In hyperferritinemic sepsis-induced multiple organ failure, the combination of hepatobiliary dysfunction and disseminated intravascular coagulation reflects reticuloendothelial system activation and defines sepsis-associated macrophage activation syndrome. In this condition profound T cell and NK cell lymphopenia with normal cytolytic activity allows free hemoglobin and pathogens to stimulate inflammasome activation in the absence of interferon γ production that is be treated with source control, IVIG, plasma exchange, and interleukin 1 receptor antagonist.