Background Cytokines have been proposed as mediators of neonatal brain injury via neuroinflammatory pathways triggered by hypoxia-ischemia. Limited data are available on cytokine profiles in larger cohorts of newborns with hypoxic-ischemic encephalopathy (HIE) undergoing therapeutic hypothermia (TH). Methods Serum cytokines IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-13, TNF-α, IFN-γ were measured in newborns with HIE at 24 and 72 hours of TH. Differences between infants with favorable (survivors with mild/no MRI injury) versus adverse outcome (death or moderate/severe MRI injury) were compared using mixed models to adjust for covariates. Results Data from 36 term newborns with HIE (favorable outcome: n=20, adverse outcome: n=16) were evaluated. Cytokines IL-1β, IL-2, IL-6, IL-8, IL-10, and IL-13 were elevated in the adverse relative to favorable outcome group at 24 hours. IL-6 remained significantly elevated in the adverse outcome group at 72 hours. IL-6 and IL-10 remained significantly associated with outcome group after controlling for covariates. Conclusion Inflammatory cytokines are elevated in HIE newborns with brain injury by MRI. In particular, IL-6 and IL-10 were associated with adverse outcomes after controlling for baseline characteristics and severity of presentation. These data suggest that cytokine response may identify infants in need of additional neuroprotective interventions.

This article provides an overview of chemistry of canakinumab as well as the phase II and phase III trials that led to approval for treatment of active SJIA. To undertake this review, the authors performed literature search using Pubmed, with keywords 'canakinumab,' 'biologic,' 'anti-IL-1B,' and 'systemic juvenile idiopathic arthritis,' focusing on publications within the last 5 years. Expert commentary: Canakinumab has shown efficacy in treatment of SJIA with active systemic features including fever. There is no evidence to suggest increased risk of macrophage activation syndrome. Its use in the treatment of chronic arthritis without active systemic features has not been approved and warrants further study.

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