Hyperinflammatory Syndrome as a Cardiac Injury Mechanism

Hemophagocytic syndrome (HPS) or hemophagocytic lymphohistiocytosis (HLH) is an acute and rapidly progressive systemic inflammatory disorder characterized by cytopenia, excessive cytokine production and hyperferritinemia. Common clinical manifestations of HLH are acute unremitting fever, lymphadenopathy, hepatosplenomegaly and multiple-organ failure. It consists of two different conditions that may be difficult to distinguish: a primary form is mostly seen in children and is caused by various mutations with genetic inheritance and a secondary HLH may be secondary to a malignant, infectious, or autoimmune/autoinflammatory stimulus without an identifiable underlying genetic trigger.^,

The hyperinflammatory immune state is caused by the absence of normal downregulation by activated macrophages and lymphocytes. Most patients with HLH have impaired cytotoxic function of natural killer (NK) cells and cytotoxic lymphocytes (CTLs), coupled with excessive activation of macrophages. Lack of feedback regulation results in excessive macrophage activity and high levels of interferon gamma and other cytokines. Excessive cytokine production by macrophages, NK cells, and CTLs is a primary mediator of tissue damage.

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