Cerebrospinal fluid levels of biopterin, nitric oxide metabolites, and immune activation markers and the clinical course of human cerebral malaria.
Cerebrospinal fluid samples from 130 children who presented with cerebral malaria were investigated to elucidate the impact of biopterin production, NO formation, and local immune activation on the clinical course of this disease. Biopterin levels were significantly lower in patients who were in a deeper coma (P = .02). Cerebrospinal fluid concentrations of NO were significantly higher in children who died than in survivors (P = .037); however, this was not the case for macrophage activation markers, neopterin, and soluble tumor necrosis factor receptor p75 (sTNFR-75). Biopterin, neopterin, and sTNFR-75 but not NO concentrations were significantly related to each other. Low biopterin levels in deep coma are compatible with an impaired local Th1 response, but the low levels could also be due to the scavenging of radicals or to decreased neurotransmitter synthesis. Local production of NO, most likely by nonimmune mechanisms, may be detrimental in cerebral malaria; however, this appears not to be the case for local Th1-mediated immune pathways.
Weiss
G
G
Department of Internal Medicine, University Hospital, University of Innsbruck, Austria. guenter.weiss@uibk.ac.at
Thuma
P E
PE
Biemba
G
G
Mabeza
G
G
Werner
E R
ER
Gordeuk
V R
VR
D001708:Biopterins / Q000134:cerebrospinal fluid*; D002675:Child, Preschool; D003128:Coma / Q000134:cerebrospinal fluid / Q000276:immunology / Q000378:metabolism; D005260:Female; D016166:Free Radical Scavengers / Q000134:cerebrospinal fluid / Q000378:metabolism; D006801:Humans; D007223:Infant; D008262:Macrophage Activation; D016779:Malaria, Cerebral / Q000134:cerebrospinal fluid*; D008297:Male; D019798:Neopterin / Q000134:cerebrospinal fluid*; D018377:Neurotransmitter Agents / Q000134:cerebrospinal fluid / Q000378:metabolism; D009569:Nitric Oxide / Q000134:cerebrospinal fluid*; D018124:Receptors, Tumor Necrosis Factor / Q000032:analysis*; D018417:Th1 Cells / Q000276:immunology
D016166:Free Radical Scavengers; D018377:Neurotransmitter Agents; D018124:Receptors, Tumor Necrosis Factor; D001708:Biopterins; D009569:Nitric Oxide; D019798:Neopterin