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Hydroxyurea interferes with antigen-dependent T-cell activation in vitro
J M Orendi1, H S Nottet, N M De Vos
1University Medical Center, Utrecht; Leiden University Medical Center, Leiden, The Netherlands. orendi@microbiology.azl.nl
Background:
Hydroxyurea is believed to inhibit human immunodeficiency virus type 1 (HIV-1) in HIV disease by decreasing the amount of intracellular deoxynucleotides needed for viral replication. A plasma concentration of 400 micromol L-1 is tolerated in oncological diseases. The present study focused on the possible interference of hydroxyurea with antigen-dependent T-cell activation as an alternative explanation for inhibiting HIV replication in vivo.
Methods:
The effect of hydroxyurea on common antigen-induced cell proliferation was studied in peripheral blood mononuclear cells (PBMC) in vitro.
Results:
Hydroxyurea inhibited Candida albicans-induced cell proliferation at a low concentration (1 micromol L-1), while at least 10 micromol L-1 was required to block HIV-1 replication in phytohaemagglutinin (PHA)-stimulated PBMC.
Conclusion:
Hydroxyurea inhibits antigen-induced lymphoproliferation in vitro at a concentration at which it does not inhibit PHA-induced HIV replication. Hydroxyurea may inhibit HIV-1 in CD4+ T cells in vivo not only by decreasing the amount of intracellular deoxynucleotides, but more specifically by interfering with antigen-dependent T-cell activation, thereby causing a reduction in the number of HIV target cells.