Hydroxyurea interferes with antigen-dependent T-cell activation in vitro.
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.


CONCLUSIONS
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.
Orendi
J M
JM
University Medical Center, Utrecht; Leiden University Medical Center, Leiden, The Netherlands. orendi@microbiology.azl.nl
Nottet
H S
HS
De Vos
N M
NM
Visser
M R
MR
Snippe
H
H
Boucher
C A
CA
Verhoef
J
J
D002176:Candida albicans / Q000276:immunology; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology*; D019259:Lamivudine / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects*; D010835:Phytohemagglutinins / Q000276:immunology; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000821:virology; D015215:Zidovudine / Q000494:pharmacology
D010835:Phytohemagglutinins; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D015215:Zidovudine; D006918:Hydroxyurea