Cerebrospinal Fluid Neopterin Levels in 159 Neurologically Asymptomatic Persons Infected with the Human Immunodeficiency Virus (HIV-1): Relationship to Immune Status

Abstract

Monocytes and brain macrophage–microglial cells are thought to play a crucial role in the neurologic dysfunction associated with HIV-1 disease. Since neopterin is produced by monocytes–macrophages, we asked whether cerebrospinal fluid (CSF) neopterin levels increase before the onset of HIV-1 neurologic disease and whether they correlate with other CSF and peripheral blood immunologic parameters. In this study, CSF neopterin levels from 159 neurologically asymptomatic HIV-positive persons were found to increase as the blood CD4⁺ T-cell count decreased and as CSF IgG, IgG synthesis, IgG index, and β₂-microglobulin increased. Neopterin levels in the CSF exceeded those in the serum in 32% of patients, while 25% had CSF levels >13.5 nmol/liter. CSF neopterin levels vary with immune status, may reflect intrathecal production, and can be elevated in asymptomatic HIV-positive patients with normal neurologic examinations. Long-term follow-up of this patient population should be able to define the clinical correlation between CSF neopterin levels during the asymptomatic phase of HIV-1 disease and the risk of subsequent neurologic disease.