CYTOKINE-STIMULATED HUMAN-IMMUNODEFICIENCY-VIRUS REPLICATION IS INHIBITED BY N-ACETYL-L-CYSTEINE

We show that the stimulation of human immunodeficiency virus (HIV) brought about by tumor necrosis factor α and phorbol 12-myristate 13-acetate can be inhibited by adding N-acetyl-L-cysteine (NAC). NAC, which replenishes intracellular glutathione, effectively inhibits the tumor necrosis factor α- or phorbol ester-stimulated replication of HIV in acutely infected cell cultures. NAC also inhibits the cytokine-enhanced HIV long terminal repeat-directed expression of β-galactosidase in in vitro HIV model systems. These results show that intracellular thiol levels influence HIV production. Furthermore, because NAC reverses tumor necrosis factor α toxicity both in cells and in animals and is a well-known drug that can be administered orally without known toxicity in humans, these results suggest that NAC is a possible therapeutic agent in AIDS.