Model of HLH pathophysiology (adapted from Brisse et al⁵ ). Dendritic cells (DCs) present antigens of various origins, and stimulate immune cell proliferation. Due to an inherited or acquired defect in degranulation and cytolysis, negative feedback regulation is disabled leading to the vicious circle of the proliferation of CD8⁺ T cells and macrophages producing organ damage and hemophagocytosis. A plethora of proinflammatory cytokines are involved with interferon-γ (IFNγ) being a central regulator of the subsequent cytokine storm (proinflammatory cytokines in red, anti-inflammatory interleukin 10 [IL10] in green). TNFα, tumor necrosis factor α.