Clinical Utility of Interleukin-1 Inhibitors in Pediatric Sepsis

Abstract

Abstract The pathophysiology of pediatric sepsis is characterized by increased innate immune activation earlier in life. Interleukin-1 is a pro-inflammatory cytokine implicated in the pathophysiology of sepsis and ferritin is a stable surrogate biomarker for elevated IL-1 levels. Data in adult sepsis has shown that use of anakinra, an anti-IL-1 receptor antagonist led to improved clinical outcomes in patients with features of macrophage activation and hyperferritinemia. However, data in pediatric sepsis is lack. Our narrative review sought to highlight the current understanding of using IL-1 inhibitors in pediatric sepsis. We identified 5 studies including 1 case report and 4 retrospective case series that described clinical outcomes in relation to use of anakinra for secondary hemophagocytic lymphohistiocytosis (HLH). A few patients in this pooled heterogenous cohort of 72 patients had concomitant infection meeting criteria for sepsis. All studies measured ferritin levels and reported a decrease in ferritin after initiating anakinra. 12 patients died after treatment initiation. There was no clear comparison in clinical outcomes between infected and non-infected patients. The pathophysiology of pediatric sepsis suggests that there is a need for blinded clinical trials using targeted immunomodulation such as IL-1 inhibitors in pediatric sepsis cohort with an immunophenotype suggesting increased innate immune activation.