Inter-relationships between quinolinic acid, neuroactive kynurenines, neopterin and β2-microglobulin in cerebrospinal fluid and serum of HIV-1-infected patients

Melvyn P. Heyes, Bruce J. Brew, Kuniaki Saito, Bonnie J. Quearry, Richard W. Price, Kristin Lee, Ravi B. Bhalla, Margaret Der, Sanford P. Markey

研究成果: Article査読

124 被引用数 (Scopus)

抄録

Quinolinic acid (QUIN) is an neurotoxic N-methyl-d-aspartate receptor agonist and an l-tryptophan metabolite of the kynurenine pathway. Increased concentrations of QUIN occur in both cerebrospinal fluid (CSF) and blood of patients infected with human immunodeficiency virus (HIV)-1, particularly those with neurologic disturbances. In the present study of HIV-1 infected patients in Walter Reed stages 4,5, and 6, reductions in l-tryptophan accompanied proportional increases in l-kynurenine and QUIN in both serum and CSF. Further, close inter-correlations exist between QUIN kynurenic acid and L-kynurenine with both β2-microglobulin and neopterin in CSF and serum. These correlations support the hypotheses that the kynurenine pathway is activated in association with inflammation and induction of indoleamine-2,3-dioxygenase. There were no relationships between CSF QUIN, l-kynurenine or kynurenic acid with the ratio of serum: CSF albumin concentrations, which indicates that the increases in CSF QUIN, l-kynurenine or kynurenic acid were not dependent on a breakdown of the blood-brain barrier. Kynurenic acid is also a kynurenine pathway metabolite that can attenuate the excitotoxic effects of QUIN when present in higher molar concentrations. While CSF kynurenic acid levels were increased in HIV-1 infected patients, the magnitude of the increases were smaller than those of QUIN and the molar concentrations of kynurenic acid were consistently lower than QUIN by at least one order of magnitude. We conclude that immune activation increases the levels of neuroactive kynurenines within the central nervous system of HIV-1 infected patients secondary to activation of indoleamine-2,3-dioxygenase.

本文言語English
ページ(範囲)71-80
ページ数10
ジャーナルJournal of Neuroimmunology
40
1
DOI
出版ステータスPublished - 09-1992
外部発表はい

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Neurology
  • Clinical Neurology

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