Increased concentrations of
excitotoxin quinolinic acid in cerebrospinal fluid (CSF) are associated with
infection with the human immunodeficiency virus (HIV-1) and have been implicated in the pathogenesis of the
acquired immune deficiency syndrome (
AIDS) dementia complex. In the present study, inoculation of macaques with D/1/California, an immunosuppressive serotype 1 type D retrovirus, was associated with acute and chronic increases in CSF and serum
quinolinic acid concentrations in macaques that had developed
SAIDS, a simian disease analogous to
AIDS in humans--particularly macaques with demonstrable
opportunistic infections.
Kynurenic acid, an antagonist of
excitatory amino acid receptors as well as the excitotoxic effects of
quinolinic acid, was also increased in the CSF of
SAIDS macaques, but to a significantly lesser degree than was
quinolinic acid (
kynurenic acid, 1.8-fold;
quinolinic acid, 15.6-fold). CSF
quinolinic acid, but not
kynurenic acid, was also increased in viremic macaques with
SAIDS-related complex (2.4-fold) and asymptomatic virus positive carriers (3.4-fold). Macaques that had recovered from D/1/California
infection and were antibody positive and virus negative had normal CSF
quinolinic acid and
kynurenic acid concentrations. Increased activity of indoleamine-2,3-dioxygenase, the first
enzyme of the
kynurenine pathway, was indicated in the macaques with
SAIDS by reduced serum
L-tryptophan and elevated serum L-
kynurenine concentrations. Macaques infected with D/1/California may provide a primate model for investigation of the mechanisms involved in increases in CSF
quinolinic acid in retrovirus and other
infectious diseases, including HIV-1. It remains to be determined whether the increased CSF
quinolinic acid concentrations and the increased ratio of
quinolinic acid to
kynurenic acid have neurological significance or are a useful "marker" of
infection.