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

Abstract

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-γ 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-1β, 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 1 pg/mL, IQR [1] vs. severe swelling 18.7 pg/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 3 pg/mL, IQR [1–20] vs. moderate swelling 24 pg/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.Electronic supplementary materialThe online version of this article (10.1186/s12936-018-2590-0) contains supplementary material, which is available to authorized users.

Cytokines in CAR T Cell–Associated Neurotoxicity

“…Some studies reported that IFNg, TNF, IL-1b, IL-4, IL-6, IL-8, IL-10, IL12p70, and/or CXCL10 were elevated in children with cerebral malaria compared to those with uncomplicated malaria (134)(135)(136), while others reported no difference in cytokine levels between the groups (137). The degree of brain swelling was independent of plasma levels of IL-1b, IL-6, IL-8, and IL-10 in children with cerebral malaria, while IL-12 and TNF were elevated in patients with more severe edema (138).…”

Systemic Inflammation Persists the First Year after Mild Traumatic Brain Injury: Results from the Prospective Trondheim Mild Traumatic Brain Injury Study

“…It may suggest that systemic low-grade inflammation in patients with mTBI reflects disease severity not obviously linked to neuroradiological findings, a fact reported in other diseases such as febrile status epilepticus and brain swelling in cerebral malaria. 39,40 Likewise, more severe injury indicated by lower GCS score was negatively associated with eotaxin and MIP-1b. Although GCS score has been shown to be an important predictor of morbidity in severe TBI, 41 it has shown relatively poor prognostic utility in mTBI, 42 and to our knowledge, its relation with inflammatory markers has not been investigated.…”

Pathophysiology and neurologic sequelae of cerebral malaria

“…For example, therapeutic sphingosine-1-phosphate (S1P) blocking agents, such as FTY720 decreased lymphocyte trafficking into the brain and lowered peripheral IFNγ levels [74]. Not all studies have found a relation between peripheral cytokines and cerebral oedema in CM [75].…”