Interleukin-16 inhibits human immunodeficiency virus type 1 entry and replication in macrophages and in dendritic cells

Recombinant interleukin-16 (rIL-16) has been found to inhibit human immunod eficiency virus type 1 (HIV-1) replication in acutely or endogenously infec ted CD4(+) T cells. However, the effect of rIL-16 on HIV-1 replication in a ntigen-presenting cells (APCs) is still unknown. We show here a potent HIV- suppressive activity of rIL-16 in acutely infected monocyte-derived macroph ages and dendritic cells determined by the levels of viral RNA transcripts or of viral reverse transcriptase in culture supernatants. The observed eff ect was dependent on the presence of rIL-16 early after infection and could not be induced by a 24-h treatment of cells with the cytokine prior to inf ection. Using macrophage;tropic and dually tropic primary isolates, we also showed that the addition of rIL-16 to cell cultures only during the infect ion period was effective in blocking virus entry and reducing proviral DNA levels in APCs. However, the anti-HIV activity of rIL-16 could not be linke d to the induction of virus-suppressive concentrations of beta-chemokines o r to the inhibition of HIV-enhancing cytokines. These findings establish a critical role for rIL-16 in protecting APCs against HIV-1 infection and len d further support to its potential use in the treatment of HIV disease.