title: Induction of inflammatory cytokines in placental monocytes of gravidae infected with the human immunodeficiency virus type 1.
abstract: Placental mononuclear cells (PMC) are susceptible to infection with the human immunodeficiency virus (HIV). PMC secreted tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta), and IL-6 among other factors, which, in turn, regulate HIV replication in latently infected cells. We assessed the induction of these cytokines in PMC from HIV-infected (HIV+) and uninfected (control) gravidae following exposure to lipopolysaccharide (LPS), HIV lysate (iHIV), recombinant HIV env (GP160) and HIV gag (gag55), and synthetic HIV p17 (HGP30) antigens. In comparison to control PMC, HIV+ PMC constitutively secreted higher levels of IL-1beta and IL-6 and were refractory to stimulation by iHIV, GP160, gag55, and HGP30. Control PMC IL-1 beta levels were boosted by LPS; gag55 and HGP30 augmented IL-6 but not IL-1 beta. Both groups exhibited 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 further augmented by LPS, yet the incremental levels were lower than those obtained from PMC of uninfected women. The high basal constitutive secretion of cytokines by HIV+ PMC and their refractoriness to activation may reflect a virus-mediated dysregulation of cytokine expression culminating in compromised host defenses against secondary opportunistic infections associated with AIDS.
authors.affiliation: Division of Laboratory Medicine, University of Texas, M.D. Anderson Cancer Center, Houston 77030, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Reuben
authors.forename: J A
authors.initials: JA
authors.lastname: Turpin
authors.forename: B N
authors.initials: BN
authors.lastname: Lee
authors.forename: M
authors.initials: M
authors.lastname: Doyle
authors.forename: B
authors.initials: B
authors.lastname: Gonik
authors.forename: R
authors.initials: R
authors.lastname: Jacobson
authors.forename: W T
authors.initials: WT
authors.lastname: Shearer
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000378:metabolism* / Q000635:transmission; D016022:Case-Control Studies; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D015497:HIV-1; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis / Q000235:genetics; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008431:Maternal-Fetal Exchange / Q000502:physiology; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D010920:Placenta / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious; D012333:RNA, Messenger / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
chemical_list: D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha