The fact that the innate immune system is strongly activated, and it releases an increased amount of IL-1 and IL-6 participating in multisystemic inflammation and the onset of MAS, has led to the administration of IL-1 blockers in the treatment of sJIA (e.g., Anakinra or canakinumab) and IL-6 inhibitors (TCZ), and giving up TNF-α inhibitory biologics, which is further evidence of an autoinflammatory process [106,107]. Here, TNF is linked to macrophage activation syndrome.