Quinolinic acid in tumors, hemorrhage and bacterial infections of the central nervous system in children.
A potential mechanism that may contribute to neurological deficits following central nervous system infection in children was investigated. Quinolinic acid (QUIN) is a neurotoxic metabolite of the kynurenine pathway that accumulates within the central nervous system following immune activation. The present study determined whether the levels of QUIN are increased in the cerebrospinal fluid of children with infections of the CNS, hydrocephalus, tumors or hemorrhage. Extremely high QUIN concentrations were found in patients with bacterial infections or the CNS, despite treatment with antimicrobial agents. CSF QUIN levels were also elevated to a lesser degree in patients with hydrocephalus or tumors. CSF L-kynurenine levels increased in parallel to the accumulations in QUIN, which is consistent with increased activity of the first enzyme of the kynurenine pathway, indoleamine-2,3-dioxygenase. The CSF levels of neopterin, a marker of immune and macrophage activation, were also increase in patients with infections. The cytokines tumor necrosis factor-alpha and interleukin-6 were also detected in some patients' samples, and were highest in patients with infection. These results suggest that QUIN is a sensitive marker of the presence of immune activation within the CNS. Further studies of QUIN as a potential contributor to neurologic dysfunction and neurodegeneration in children with CNS inflammation are warranted.
Heyes
M P
MP
Section on Analytical Biochemistry, National Institute of Mental Health, Bethesda, MD 20892, USA.
Saito
K
K
Milstien
S
S
Schiff
S J
SJ
D000293:Adolescent; D000328:Adult; D001424:Bacterial Infections / Q000378:metabolism*; D015415:Biomarkers / Q000737:chemistry; D001708:Biopterins / Q000031:analogs & derivatives / Q000032:analysis; D002493:Central Nervous System Diseases / Q000378:metabolism* / Q000382:microbiology; D016543:Central Nervous System Neoplasms / Q000737:chemistry*; D002543:Cerebral Hemorrhage / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006160:Guanosine Triphosphate / Q000378:metabolism; D006801:Humans; D006849:Hydrocephalus / Q000378:metabolism; D007223:Infant; D007231:Infant, Newborn; D015850:Interleukin-6 / Q000032:analysis; D007737:Kynurenine / Q000032:analysis; D008297:Male; D019798:Neopterin; D017378:Quinolinic Acid / Q000032:analysis*; D014366:Tryptophan Oxygenase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D015415:Biomarkers; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D001708:Biopterins; D007737:Kynurenine; D019798:Neopterin; D006160:Guanosine Triphosphate; D014366:Tryptophan Oxygenase; D017378:Quinolinic Acid