Frontal cortex indoleamine-2,3-dioxygenase activity is increased in HIV-1-associated dementia.

HIV-associated dementia is a frequent consequence of HIV infection and relates to neuronal damage, possibly as a result of increased neurotoxic kynurenine metabolites. Indoleamine-2,3-dioxygenase (IDO) activity, which regulates kynurenine metabolism, may thus be increased in HIV infection. We measured IDO activity in post-mortem brain tissue from AIDS patients, including a subgroup that exhibited dementia, and age-matched control subjects. IDO activity was increased, but not significantly, in the AIDS group as well as the non-dementia group, compared to controls. Enzyme activity was significantly increased in the dementia group when compared to control values. IDO activity is increased in HIV-associated dementia and is thus likely to increase kynurenine pathway metabolites, such as 3-hydroxykynurenine and quinolinic acid, and elevated levels of these neurotoxins may contribute to the neuronal deficits underlying HIV-associated dementia.