STAT1 modulates HIV-1–induced up-regulation of IL-6 expression in HBMECs. (A) Interaction of HBMECs with HIV-infected MDMs induced IL-6 secretion in HBMECs. Coculture of HBMECs with infected MDMs increased IL-6 expression/secretion in endothelial cells by 10-fold (229.2 ± 38 pg/mL) compared with endothelial cells cocultured with noninfected MDMs (23 ± 3 pg/mL). Endothelial-MDM coculture did not change MDM IL-6 levels regardless of HIV-1 infection. (B) Direct exposure of HBMECs to 0.01 infectious viral particles induced a time-dependent increase in IL-6 secretion. (C) Fludarabine (FLUD, 20 μM) significantly diminished HIV-1–induced IL-6 secretion in HBMECs. Controls are untreated cells; NI-control represents HBMECs exposed for 24 hours to conditioned media from noninfected MDMs. For each experimental condition, the number of replicates is 6. (***P < .001 compared with controls.) TM indicates top media; BM, bottom media; CM, conditioned media; NI-MDM, noninfected monocyte-derived macrophage; HIV-MDM, HIV-infected monocyte-derived macrophage; and MOI, multiplicity of infection.