Effect of simian immunodeficiency virus infection on tumor necrosis factor-α production by alveolar macrophages

C. J. Horvath, R. C. Desrosiers, P. K. Sehgal, N. W. King, D. J. Ringler

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

We studied the release of tumor necrosis factor-α (TNFα), a vital immunoregulatory cytokine, by alveolar macrophages (M∅s) infected with simian immunodeficiency virus (SIV) in vitro or collected from SIV-infected macaques. For in vitro studies, M∅s were harvested by bronchoalveolar lavage from 5 normal animals and infected in flasks with SIV (104TCID50/2.5 x 106 M∅s). After 7 to 10 days, cytopathic effect was prominent and 68 ± 2% of M∅s were immunoreactive for p27 core protein. Uninfected (control) and SIV-infected M∅s were then cultured for 24 hours in 96-well plates (105 M∅s/well) while challenged with lipopolysaccharide (LPS; 100 μg/ml). TNFα was assayed in culture supernatants by an enzyme-linked immunosorbent assay (detection limit, 50 pg/ml) and results were expressed as pg TNFα/ml/103 M∅s (mean ± SEM). TNFα was not detected in unstimulated wells. TNFα release by control and SIV-infected M∅s was similar (6.6 ± 0.7 and 7.9 ± 1.1 pg/ml/103 M∅s, respectively). We also studied TNFα release by alveolar M∅s from 8 animals infected with SIV (3 asymptomatic, 5 with acquired immune deficiency syndrome virus (AIDS)). One animal with AIDS had p27+ M∅s. Alveolar M∅s from asymptomatic animals released significantly more TNFα (10.3 ± 1.1 pg/ml/103 M∅s) than did animals with AIDS or uninfected macaques (5.2 ± 0.8 and 7.0 ± 0.6 pg/ml/103 M∅s, respectively (p < 0.01). However, M∅s from monkeys with AIDS failed to respond to LPS after 7 to 10 days in culture. In summary, in vitro infection with SIV does not cause constitutive TNFα release or alter the response of cultured M∅s to LPS. When kep in culture, M∅s collected from asymptomatic, SIV-infected animals retain their response to LPS, whereas M∅s from animals with AIDS lose the capacity to produce TNFα. Furthermore, M∅s cytokine production is exaggerated before overt clinical disease, but not as a direct result of infection with SIV.

Original languageEnglish (US)
Pages (from-to)280-286
Number of pages7
JournalLaboratory Investigation
Volume65
Issue number3
StatePublished - 1991
Externally publishedYes

Keywords

  • AIDS
  • Alveolar
  • Cytokine
  • HIV

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

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