TNF and macrophage activation syndrome: In secondary HLH, also called macrophage activation syndrome (MAS, Macrophage activation syndrome) or more precisely macrophage activation-like syndrome (MALS), it is believed that hyperproduction of cytokines [specifically, IL-1β, interferon-γ (INF-γ), tumor necrosis factor alpha, soluble IL-2 receptor (CD25), IL-12] leads to the depletion of NK cells and cytotoxic T lymphocytes, accompanied by the activation of tissue macrophages that produce pro-inflammatory cytokines (IL-1, IL-6, IL-10 and IL-18).