AIDSWEEKLY Plus, Monday, 28 July 1997
Daniel J. DeNoon, Senior Editor
Interleukin 16 (IL-16) corrects some of the functional defects seen in HIV infected cells.
The cytokine may thus have a therapeutic role in combination with IL-2, intermittent doses of which increase CD4(+) T-cell counts in people with HIV infection.
"We hypothesize that IL-16 may be a useful adjunct to IL-2 for immune reconstitution therapy of HIV-1 infected individuals, increasing the number of CD4(+) T cells while at the same time suppressing viral replication," suggested Nereida A. Parada and colleagues of the Boston University School of Medicine, Boston, Massachusetts.
Parada reported data from a study of the synergistic effects of IL-16 and IL-2 in a poster presentation to "New Opportunities for HIV Therapy - From Discovery to Clinical Proof-of-Concept," the 2nd Joint Conference of the National Institute of Allergy and Infectious Diseases (NIAID) Strategic Program for Innovative Research on AIDS Treatment (SPIRAT) and the National Cooperative Drug Discovery Groups for the Treatment of HIV Infection (NCDDG-HIV), held June 22-26, 1997, in Vienna, Virginia.
Noting that IL-16 selectively induces CD4(+) T-cell expression of IL-2 receptors - while suppressing HIV replication - Parada et al. explored the in vitro effects of combined IL-16 and IL-2 on peripheral blood mononuclear cells (PBMC) infected with HIV-1.
In both normal and HIV-1 infected PBMCs, IL-16 synergistically increased IL-2 upregulation of thymidine uptake over four days.
Over four weeks of culture, IL-16 and IL-2 expanded CD4(+) populations. These expanded populations had several interesting features:
* The expanded population was made up of cells bearing the CD4(+)CD25(+)CD45RO(+) phenotype. These cells were able to synthesize both T-helper type 1 (Th1) and Th2 cytokines.
* In response to anti-CD3 antibodies and recall antigens, the expanded CD4(+) T-cell population proliferated normally.
* In the presence of IL-16, the expanded cells did not exhibit HIV associated down-regulation of bcl-2.
"Therefore, the increase in total cells in IL-16/IL-2 treated cultures may occur as a result of increased cell proliferation and reduction in apoptosis," Parada et al. concluded.
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