Therapy of 'SHIV' infected macaques with liposomes delivering antisense interleukin-4 DNA

Background/objectives: To explore the effects of antisense (AS) interleukin (IL)-4 on virus replication and CD8(+) T-cell responses in lymph nodes and blood of macaques infected with simian human immunodeficiency virus, SHIV89.6P. Methods: Six macaques were inoculated with simian human immunodeficiency virus (SHIV89.6P). Seven days later, four of the animals were given 1 mg AS IL-4 plasmid complexed with Megafectin liposome, intravenously, and two of these received a second injection of the same material on day 9. All six macaques were killed at 2 weeks post infection (pi) and monitored for viral RNA and CD8(+) T cells in blood and lymph nodes by real-time reverse transcriptase-polymerase chain reaction, flow cytometry and immunohistochemistry. Results: In contrast to the lymph nodes from virus control animals, the lymph nodes of AS IL-4-treated animals had a significant reduction in viral loads and reduced depletion of cells from the nodes. There was an increase in CD8(+) T cells in the nodes, and many of the cells expressed granzyme B, suggesting functional activation. This trend of virus reduction and increased CD8(+) T cell numbers was also reflected in blood. Conclusions: The therapeutic effect of the AS IL-4 suggests indirectly that the acute immunosuppressive disease caused by SHIVs is mediated, in part, by IL-4 that causes enhanced virus replication by suppressing anti-viral CD8(+) T-cell responses, and that this effect was reduced by treatment of the animals with AS IL-4.