ALPHA-LIPOIC ACID IS A POTENT INHIBITOR OF NF-KAPPA-B ACTIVATION IN HUMAN T-CELLS

Acquired immunodeficiency syndrome (AIDS) results from infection with a human immunodeficiency virus (HIV). The long terminal repeat (LTR) region of HIV proviral DNA contains binding sites for nuclear factor κB (NF-κB), and this transcriptional activator appears to regulate HIV activation. Recent findings suggest an involvement of reactive oxygen species (ROS) in signal transduction pathways leading to NF-κB activation. The present study was based on reports that antioxidants which eliminate ROS should block the activation of NF-κB and subsequently HIV transcription, and thus antioxidants can be used as therapeutic agents for AIDS. Incubation of Jurkat T cells (1 × 106 cells/ml) with a natural thiol antioxidant, α-lipoic acid, prior to the stimulation of cells was found to inhibit NF-κB activation induced by tumor necrosis factor-α (25 ng/ml) or by phorbol 12-myristate 13-acetate (50 ng/ml). The inhibitory action of α-lipoic acid was found to be very potent as only 4 mM was needed for a complete inhibition, whereas 20 mM was required for N-acetylcysteine. These results indicate that α-lipoic acid may be effective in AIDS therapeutics. © 1992.