Induction of inflammatory cytokines in placental monocytes of gravidae infected with the human immunodeficiency virus type 1

James M. Reuben, Jim A. Turpin, Bang Ning Lee, Marilyn Doyle, Bernard Gonik, Robert Jacobson, William T. Shearer

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Abstract

Placental mononuclear cells (PMC) are susceptible to infection with the human immunodeficiency virus (HIV). PMC secreted tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), 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-1β and IL-6 and were refractory to stimulation by iHIV, GP160, gag55, and HGP30. Control PMC IL-1β levels were boosted by LPS; gag55 and HGP30 augmented IL-6 but not IL-1β. Both groups exhibited low basal TNF-α production that was augmented by LPS. HIV+ PMC exhibited higher constitutive levels of IL-1β, IL-6, and TNF-α 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.

Original languageEnglish (US)
Pages (from-to)963-971
Number of pages9
JournalJournal of Interferon and Cytokine Research
Volume16
Issue number11
DOIs
StatePublished - Nov 1996

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ASJC Scopus subject areas

  • Immunology
  • Cell Biology
  • Virology

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