QUINOLINIC ACID IN TUMORS, HEMORRHAGE AND BACTERIAL-INFECTIONS OF THECENTRAL-NERVOUS-SYSTEM IN CHILDREN

A potential mechanism that may contribute to neurological deficits fol lowing central nervous system infection in children was investigated. Quinolinic acid (QUIN) is a neurotoxic metabolite of the kynurenine pa thway that accumulates within the central nervous system following imm une activation. The present study determined whether the levels of QUI N 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 wer e also elevated to a lesser degree in patients with hydrocephalus or t umors. CSF L-kynurenine levels increased in parallel to the accumulati ons 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, we re also increase in patients with infections. The cytokines tumor necr osis factor-ct and interleukin-6 were also detected in some patients' samples, and were highest in patients with infection. These results su ggest that QUIN is a sensitive marker of the presence of immune activa tion within the CNS. Further studies of QUIN as a potential contributo r to neurologic dysfunction and neurodegeneration in children with CNS inflammation are warranted.