Cerebrospinal fluid cytokine levels and cognitive impairment in cerebral malaria

Abstract

Cerebrospinal fluid (CSF) and serum levels of 12 cytokines or chemokines important in central nervous system (CNS) infections were measured in 76 Ugandan children with cerebral malaria (CM) and 8 control children. As compared with control children, children with cerebral malaria had higher cerebrospinal fluid levels of interleukin (IL)-6, CXCL-8/IL-8, granulocyte-colony stimulating factor (G-CSF), tumor necrosis factor-alpha (TNF-alpha), and IL-1 receptor antagonist. There was no correlation between cerebrospinal and serum cytokine levels for any cytokine except G-CSF. Elevated cerebrospinal fluid but not serum TNF-alpha levels on admission were associated with an increased risk of neurologic deficits 3 months later (odds ratio 1.55, 95% CI: 1.10, 2.18, P = 0.01) and correlated negatively with age-adjusted scores for attention (Spearman rho, -0.34, P = 0.04) and working memory (Spearman rho, -0.32, P = 0.06) 6 months later. In children with cerebral malaria, central nervous system TNF-alpha production is associated with subsequent neurologic and cognitive morbidity.

FIGURE 1

CSF levels (pg/mL) of 12 cytokines and chemokines in 76 Ugandan children with cerebral malaria (CM) and 8 North American children without neurologic disease. Lines depict median values in each group. For all values depicted on a log scale, undetectable cytokine levels were given a value of 0.1 pg/mL, or 10^-1 pg/mL. The following outlier values (pg/mL) are not depicted: G-CSF, 14268.2; IL-1β, 2,951.7; IL-1ra, 21960.4; IL-6, 2,3371.4; IL-10, 1,036.7; TNF-α, 688.8; CCL3/MIP-1α, 2,302.6; CCL4/MIP-1β, 20,909.4.