Quinolinic acid (QUIN) is an excitotoxic tryptophan and kynurenine pathway metabolite that has been implicated in the etiology of many neurologic disease. We have discovered that the most pronounced increases in brain and cerebrospinal fluid QUIN levels occur in patients with inflammatory neurologic diseases, including patients infected with the human immunodeficiency syndrome. The mechanisms involved in increasing QUIN synthesis from L-tryptophan include induction of indoleamine-2,3-dioxygenase, kynurenine-3-hydroxylase, kynureninease and 3-hydroxyanthranilate-3,4-dioxygenase. Macrophages have a high capacity to convert L-tryptophan to QUIN and such cells may be a predominant source of QUIN in the central nervous system of patients with inflammatory neurologic diseases. Strategies to attenuate the synthesis of QUIN or attenuate its stimulatory effects on the N-methyl-D-aspartate receptors which mediate its neurologic effects are potentially new approaches to the therapy of inflammatory neurologic diseases.
