The proinflammatory cytokine IL-18 is elevated in both normal neonates and those with sepsis, in whom it has a deleterious role. In the Proceedings of the National Academy of Sciences USA, Moore and colleagues use a neonatal mouse model of polymicrobial sepsis to investigate the mechanistic basis of IL-18's function in sepsis. IL-18-deficient mice are resistant to sepsis, and exogenous supply of this cytokine worsens the outcome of sepsis, increases the bacterial load in the peritoneum and manifests as damage to the gut ileum. Mechanistically, IL-18 activates secretion of the proinflammatory cytokine IL-17A by γδ T cells, and it is this that worsens symptoms in this model of sepsis. These data reveal an unexpected pathway involved in the pathology of neonatal sepsis and might lead to new drug targets in this otherwise nearly intractable condition.
About this article
Cite this article
Fehervari, Z. Neonatal sepsis. Nat Immunol 17, 617 (2016). https://doi.org/10.1038/ni.3475