INDUCTION OF INFLAMMATORY CYTOKINES IN PLACENTAL MONOCYTES OF GRAVIDAE INFECTED WITH THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1

Placental mononuclear cells (PMC) are susceptible to infection with th e human immunodeficiency virus (HIV), PMC secreted tumor necrosis fact or-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and IL-6 among o ther factors, which, in turn, regulate HIV replication in latently inf ected cells, We assessed the induction of these cytokines in PMC from HIV-infected (HIV+) and uninfected (control) gravidae following exposu re to lipopolysaccharide (LPS), HIV lysate (iHIV), recombinant HIV env (GP160) and HIV gag (gag55), and synthetic HIVp17 (HGP30) antigens, I n comparison to control PMC, HIV+ PMC constitutively secreted higher l evels of IL-1 beta and IL-6 and were refractory to stimulation by iHIV , GP160, gag55, and HGP30, Control PMC IL-1 beta levels were boosted b y LPS; gag55 and HGP30 augmented IL-6 but not IL-1 beta, Both groups e xhibited low basal TNF-alpha production that was augmented by LPS, HIV + PMC exhibited higher constitutive levels of IL-1 beta, IL-6, and TNF -alpha gene transcription than control PMC, These levels could be furt her augmented by LPS, yet the incremental levels were lower than those obtained from PMC of uninfected women, The high basal constitutive se cretion of cytokines by HIV+ PMC and their refractoriness to activatio n may reflect a virus-mediated dysregulation of cytokine expression cu lminating in compromised host defenses against secondary opportunistic infections associated with AIDS.