Hyperinflammation: On the pathogenesis and treatment of macrophage activation syndrome

Macrophage activation syndrome (MAS) is a subtype of hemophagocytic lymphohistiocytosis (HLH) diseases. The underlying mechanism these life-threatening disorders impaired granule-mediated cytotoxicity exerted by natural killer (NK) cells and T lymphocytes. This function meant for elimination virus-infected cells, malignant to prevent exaggerated immune responses. normal outcome after an attack NK or cytotoxic apoptosis the target cell. prevents inflammatory responses in adjacent tissues which occur lytic cell death. Extensive lysis can even produce cytokine storm, as evidenced MAS. Programmed proinflammatory death, pyroptosis, caused activated inflammasomes central pathogenesis Pyroptosis mediates IL-18 release, robustly stimulates IFN-γ, key macrophage-activating signal initiates burst cytokines chemokines. Lytic death also discharge prototype alarmin high mobility group box protein 1 (HMGB1), molecule present all that MAS outlined here. Therapeutic options control causal factors operating are discussed.