Brain swelling is independent of peripheral plasma cytokine levels in Malawian children with cerebral malaria

BackgroundCerebral malaria (CM) is often fatal, and severe brain swelling is a predictor of CM-related mortality. CM is characterized by elevated circulating pro-inflammatory cytokines TNF and IFN- and anti-inflammatory cytokine IL-10, however whether cytokine levels correlate with brain swelling severity is unknown. This study therefore was conducted to investigate the relationship between cytokine levels and brain swelling severity in children presenting with CM.MethodsA total of 195 Malawian children presenting with CM were recruited and had the concentrations of plasma cytokines determined and compared to brain swelling severity, determined by MRI examination, and graded as severe, moderate, mild or none.ResultsLevels of IL-1, IL-6, IL-8 and IL-10 did not differ between CM patients with and without severe brain swelling. Compared to children without brain swelling, IL-12 levels were higher in children with severe swelling (p<0.01, no swelling 1pg/mL, IQR [1] vs. severe swelling 18.7pg/mL, IQR [1-27]), whereas TNF concentrations were higher in children with moderate brain swelling compared to children with no swelling (p<0.01, no swelling 3pg/mL, IQR [1-20] vs. moderate swelling 24pg/mL, IQR [8-58]. Multivariate analysis showed that no single cytokine independently predicted brain swelling.ConclusionSevere brain swelling in paediatric CM was independent of tested blood pro-inflammatory and anti-inflammatory cytokines which are markers of systemic inflammation.