Selective cytotoxicity of lithium gamma-linolenic acid in human T cells chronically and productively infected with HIV.
We sought to extend observations of lithium gamma-linolenic acid (LiGLA)-associated selective cytotoxicity in different models of chronic HIV infection in vitro. In our initial experiments, 8E5, 8E5L and A3.01 cells were allowed to proliferate in the presence of 0-20 microg/ml LiGLA for 4 days. Similarly, OM-10.1 cells (with or without prior stimulation with tumour necrosis factor-alpha (TNF-alpha)) were grown with 0-5 microg/ml LiGLA for 10 days. Significant cytotoxicity was observed in productively infected 8E5 cells (100% cell death by day 2 at the highest concentration) as compared with latently infected 8E5L cells (50% cell death on days 2-4) and uninfected A3.01 cells. No drug-induced viral stimulation was observed in surviving cells. In fact, a mild direct antiviral effect may be present, independent of cytotoxicity. Maximum cytotoxicity to OM-10.1 cells was only observed when active viral replication was induced by TNF-alpha. Our preliminary results are encouraging and suggest that LiGLA should be retained as a candidate antiretroviral agent. Further work is underway to identify the specific mechanism underlying our observations.
Mpanju
O
O
British Columbia Centre for Excellence in HIV/AIDS, St Paul's Hospital, Vancouver, Canada.
Winther
M
M
Manning
J
J
Craib
K
K
Montaner
J
J
O'Shaugnessy
M
M
Conway
B
B
D019380:Anti-HIV Agents / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006678:HIV / Q000187:drug effects*; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects* / Q000821:virology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D017965:gamma-Linolenic Acid / Q000494:pharmacology*
D019380:Anti-HIV Agents; D014409:Tumor Necrosis Factor-alpha; D017965:gamma-Linolenic Acid