Ascorbate effect on cytokine stimulation of HIV production.
We have recently shown that ascorbic acid (AA) suppresses the production of HIV in a latently infected T-lymphocytic cell line (ACH-2) following stimulation with the tumor promoter, PMA. To evaluate the effect of ascorbic acid on virus activation following treatment with inflammatory cytokine, we tested tumor necrosis factor alpha (TNF-alpha) whose levels are elevated in patients with HIV/AIDS. ACH-2 cultures, pretreated with various nontoxic concentrations of ascorbate or AZT were stimulated for 2 h with TNF-alpha, and incubated further with fresh supplements of ascorbate or AZT. At 24 to 48 h post-treatment, the RT activity released into culture supernatant was determined. Results showed that TNF-alpha alone caused approximately 13- to 16-fold stimulation in the level of extracellular RT. Pretreatment with ascorbic acid at 200 micrograms/ml caused a little more than about 2- to 4-fold reduction in extracellular RT levels. Most remarkably, exposure to 300 micrograms/ml ascorbate resulted in approximately 5- to 10-fold lowering of the extra-cellular RT titer. In contrast, no significant suppression in extracellular RT levels was seen with concentrations of AZT in the range of 1-5 micrograms/ml.
Harakeh
S
S
Virology and Immunodeficiency Research Program, Linus Pauling Institute of Science and Medicine, Palo Alto, California 94306, USA.
Jariwalla
R J
RJ
D001205:Ascorbic Acid / Q000494:pharmacology*; D002460:Cell Line; D006678:HIV / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism; D013601:T-Lymphocytes / Q000821:virology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D015215:Zidovudine / Q000494:pharmacology
D014409:Tumor Necrosis Factor-alpha; D015215:Zidovudine; D012194:RNA-Directed DNA Polymerase; D013755:Tetradecanoylphorbol Acetate; D001205:Ascorbic Acid