Selective Reversal of IL-1-Mediated Cytokine Storm Using Anakinra for Sepsis-Induced MODS

Introduction: Cytokine storm syndromes are life threatening and can be triggered by multiple conditions, including sepsis. Anakinra is a recombinant IL-1 receptor antagonist, typically used to treat inflammatory diseases like systemic juvenile idiopathic arthritis, that has been demonstrated to have positive effect when used in settings of severe inflammation. Previous studies have shown that IL-1 blockade is useful in reversing effects of cytokine storm syndromes when other modalities have failed. Furthermore, studies have demonstrated a relationship between IL-1 signaling and IL-6 levels, which demonstrated a dose-dependent survival benefit in patients with septic shock, with Gram-negative infection, and in patients with an IL-6 level > 100 pg/mL at study entry. In this case, we present a patient with culture negative sepsis who improved following anakinra administration.


Description: A previously healthy 9-year-old female admitted to the pediatric ICU for increased work of breathing from apparent human metapneumovirus-associated pneumonia with rapid progression to multiple organ dysfunction syndrome (MODS). She was resuscitated with crystalloid and colloid fluids and inotrope administration of epinephrine and dobutamine. She remained hypotensive with poor perfusion and was cannulated onto veno-arterial extracorporeal life support (ECLS) for refractory shock. She was empirically administered anakinra for the presumed cytokine storm, with improvement in organ dysfunction. In addition to ECLS and anakinra, she received a 3-day course of therapeutic plasma exchange (TPE) for thrombocytopenia-associated multiple organ failure (TAMOF). Post hoc cytokine analysis revealed that anakinra administration was associated with marked decreases in IL-6 and IL-8 (CXCL8) levels, but not other cytokine biomarkers. Her ECLS was discontinued on day 5, she was extubated on day 8 and discharged to rehab on day 20.


Discussion: In this case, anakinra seemed to specifically decrease IL-6 and IL-8 levels, while not affecting CXCL9, IL-2RA, IL-18, nor TNFR1 levels. This case highlights the positive function of anakinra use during systemic inflammation conditions and its effect on IL-6 and IL-8, potential chief biomarkers of IL-1 signaling activity.