Interleukin (IL)-7 is an attractive candidate for immunotherapy in patients infected with HIV-1, according to investigators at the National Institute of Allergy and Infectious Diseases. Their recent experiments, reported in the online February 5th PNAS Early Edition, also show that IL-7 may be most effective in patients with the greatest degree of immune suppression.
Dr. Paolo Lusso and associates in Bethesda, Maryland, isolated peripheral blood mononuclear cells (PBMCs) from 24 patients at different stages of HIV-1 infection.
To assess apoptosis, they measured annexin V, which preferentially binds to dying cells, and caspase C activation, which occurs during apoptosis. When untreated PBMCs were incubated ex vivo for 7 days, annexin V binding increased dramatically (p < 0.0001).
In contrast, when cells were incubated with IL-7 for 7 days, annexin V binding decreased significantly for up to 6 days, compared with untreated cells (p < 0.0001). During the same period, caspase 3 activation decreased when cells were incubated with IL-7 (p = 0.01).
The investigators observed that the kinetics and magnitude of IL-7's effects varied markedly among patients. Peak reduction in apoptosis ranged from 5.1% to 28.4%, and occurred anywhere between 1 and 6 days. In some samples, the cytokine's effect increased over time, while it decreased in other samples.
Dr. Lusso's group evaluated several demographic, clinical, and immunologic parameters that could have affected IL-7's anti-apoptotic effect. The only factor that played a role was the severity of immune dysfunction; there was a significant inverse correlation between circulating CD4 count and IL-7's efficacy (p = 0.0099).
Similar efficacy was observed when IL-7 was incubated with purified CD4+ and CD8+ cells. IL-7 was equally effective in protecting naïve and memory T cells.
The authors saw no evidence of increased endogenous HIV-1 replication.
"The results of the present study provide a further rationale for consideration of IL-7 as a potential adjuvant therapy in HIV-1-infected individuals in association with antiretroviral therapy," Dr. Lusso and his associates conclude.
Proc Natl Acad Sci USA 2007.
Copyright
© 2007 Reuters Limited. All rights reserved. Republication or
redistribution of Reuters content, including by framing or similar
means, is expressly prohibited without the prior written consent of
Reuters. Reuters shall not be liable for any errors or delays in the
content, or for any actions taken in reliance thereon. Reuters and the
Reuters sphere logo are registered trademarks and trademarks of the
Reuters group of companies around the world.
