Effect of anakinra on cytokine storm during sepsis-induced multiple organ dysfunction syndrome: case report and preclinical investigation.

We describe the case of a young female who presented with apparent human metapneumovirus-associated illness and dehydration, but whose condition rapidly worsened with progression to multiple organ dysfunction syndrome (MODS). Multiple modalities were used to treat the patient, including: 1) extracorporeal life support (ECLS) for refractory shock; 2) anakinra, a human recombinant interleukin (IL)-1 receptor antagonist, for presumed cytokine storm; and 3) therapeutic plasma exchange (TPE) for thrombocytopenia-associated multiple organ failure (TAMOF). The patient's organ dysfunction rapidly improved. Post hoc cytokine analysis revealed that anakinra administration was associated with marked decreases in interleukin (IL)-6 and IL-8 levels, but not in other cytokine biomarkers, indicating a possible upstream IL-1 effect on IL-6/IL-8 levels. Preclinical cytokine-based sepsis models were used to investigate this possibility. The preclinical results suggest that IL-6 levels are a function of synergistic IL-1 and tumor necrosis factor (TNF) activity. Further study is needed to determine appropriate patient populations, timing, and dosing of anakinra for suppressing IL-1 signaling during cytokine storm-induced MODS.