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SM Hammer, JM Gillis, P Pinkston and RM Rose
Department of Medicine, New England Deaconess Hospital, Boston, MA 02215.
The alveolar macrophage (AM), as a representative human tissue macrophage,
was used in an in vitro system to examine the anti-human immunodeficiency
virus type-1 (HIV-1) activity of zidovudine (AZT) and
granulocyte-macrophage colony-stimulating factor (GM-CSF). AMs were
infected with the IIIB strain of HIV-1 and exposed to AZT (1 mumol/L),
GM-CSF (30 U/mL), a combination of AZT (1 mumol/L)/GM-CSF (30 U/mL), or
medium control. At 10 or 20 days post-infection, phytohemagglutinin
(PHA)-stimulated peripheral blood mononuclear leukocytes (PBMLs) were added
to the AM cultures as stimulated target cells. AZT effectively suppressed
HIV replication and prevented transfer/amplification in target PBMLs as
long as the drug was maintained in the medium. GM-CSF neither suppressed
nor augmented HIV replication. The combination of AZT/GM-CSF was comparable
with AZT alone in suppressing both the initial infection of AMs and the
transfer to target PBMLs as long as the agents were maintained in the
cultures. However, when the drugs were removed at the same time that
PHA-stimulated PBMLs were added to the culture, the combination of
AZT/GM-CSF was found to be more effective than AZT alone in preventing the
transfer/amplification of HIV in the target lymphocytes. These results
suggest that (1) AZT is effective in inhibiting HIV-1 infection in
mononuclear phagocytes; (2) GM-CSF neither inhibits nor augments the
replication of the IIIB strain of HIV in human AMs; and (3) the combination
of AZT and GM-CSF may have an enhanced anti-HIV-1 activity compared with
AZT alone. Clinical trials with the two agents in combination appear
warranted.
This article has been cited by other articles:
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| Copyright © 1990 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
