Elevated alpha–tumor necrosis factor levels in spinal fluid from HIV‐1–infected patients with central nervous system involvement

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Abstract
To assess the role of alpha–tumor necrosis factor in the pathogenesis of central nervous system involvement during human immunodeficiency virus type 1 infection, we recorded clinical data and measured alpha–tumor necrosis factor levels in serum and cerebrospinal fluid samples from 45 patients infected with human immunodeficiency virus type 1, classified as group II/III (10), group IV A (5), group IV B (10), and group IV C‐1 (20) of the Centers of Disease Control acquired immunodeficiency syndrome classification system and 42 controls. Alpha–tumor necrosis factor was above the limit of detection in only 3 of 15 sera and 3 of 15 cerebrospinal fluid samples from patients in group II/III and group IV A, whereas it was detected in 17 of 30 sera (p < 0.05) and 22 of 30 cerebrospinal fluid (p < 0.0002) samples from clinically more advanced patients (group IV B and group IV C‐1). Alpha–tumor necrosis factor mean values were 21.5 pg/ml in sera and 50.0 pg/ml in cerebrospinal fluid from group IV B patients and 30.4 pg/ml in sera and 24 pg/ml in cerebrospinal fluid from group IV C‐1 patients. In 15 of 19 (79%) patients with human immunodeficiency virus type 1 encephalopathy (group IV B, 9 of 10 patients) and with opportunistic infections of the central nervous system (groupIV C‐1, 6 of 9 patients), alpha–tumor necrosis factor levels were more elevated in cerebrospinal fluid (mean value, 42 pg/ml) than in serum (mean value,20.7 pg/ml), whereas the opposite (p < 0.002) was found in 6 of 7 (86%) patients with systemic opportunistic infections not involving the central nervous system (serum mean value, 38.9 pg/ml vs. cerebrospinal fluid mean value, 15.0 pg/ml). No correlation was found between elevated alpha–tumor necrosis factor levels and clinical evidence of dementia or central nervous system demyelination. We conclude that intrathecal production of alpha–tumor necrosis factor occurs during central nervous system localization of human immunodeficiency virus type 1 infection. Alpha–tumor necrosis factor elevation seems to be related to active infection/inflammation. Measurement of cerebrospinal fluid alpha–tumor necrosis factor levels may thus represent a useful marker for ongoing central nervous system localization of human immunodeficiency virus type 1 infection.