Inter-relationships between quinolinic acid, neuroactive kynurenines, neopterin and β 2 -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

Research output: Contribution to journalArticle

118 Citations (Scopus)

Abstract

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 β 2 -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.

Original languageEnglish
Pages (from-to)71-80
Number of pages10
JournalJournal of Neuroimmunology
Volume40
Issue number1
DOIs
Publication statusPublished - 01-01-1992
Externally publishedYes

Fingerprint

Quinolinic Acid
Kynurenine
Neopterin
Kynurenic Acid
Cerebrospinal Fluid
HIV-1
Serum
Indoleamine-Pyrrole 2,3,-Dioxygenase
Tryptophan
Blood-Brain Barrier
Nervous System
Albumins
Central Nervous System
Inflammation

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Neurology
  • Clinical Neurology

Cite this

Heyes, Melvyn P. ; Brew, Bruce J. ; Saito, Kuniaki ; Quearry, Bonnie J. ; Price, Richard W. ; Lee, Kristin ; Bhalla, Ravi B. ; Der, Margaret ; Markey, Sanford P. / Inter-relationships between quinolinic acid, neuroactive kynurenines, neopterin and β 2 -microglobulin in cerebrospinal fluid and serum of HIV-1-infected patients In: Journal of Neuroimmunology. 1992 ; Vol. 40, No. 1. pp. 71-80.
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abstract = "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 β 2 -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.",
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Inter-relationships between quinolinic acid, neuroactive kynurenines, neopterin and β 2 -microglobulin in cerebrospinal fluid and serum of HIV-1-infected patients . / Heyes, Melvyn P.; Brew, Bruce J.; Saito, Kuniaki; Quearry, Bonnie J.; Price, Richard W.; Lee, Kristin; Bhalla, Ravi B.; Der, Margaret; Markey, Sanford P.

In: Journal of Neuroimmunology, Vol. 40, No. 1, 01.01.1992, p. 71-80.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Inter-relationships between quinolinic acid, neuroactive kynurenines, neopterin and β 2 -microglobulin in cerebrospinal fluid and serum of HIV-1-infected patients

AU - Heyes, Melvyn P.

AU - Brew, Bruce J.

AU - Saito, Kuniaki

AU - Quearry, Bonnie J.

AU - Price, Richard W.

AU - Lee, Kristin

AU - Bhalla, Ravi B.

AU - Der, Margaret

AU - Markey, Sanford P.

PY - 1992/1/1

Y1 - 1992/1/1

N2 - 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 β 2 -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.

AB - 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 β 2 -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.

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