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

Citation
Jm. Orendi et al., Hydroxyurea interferes with antigen-dependent T-cell activation in vitro, EUR J CL IN, 30(2), 2000, pp. 162-166
Citations number
12
Language
INGLESE
art.tipo
Article
Categorie Soggetti
General & Internal Medicine","Medical Research General Topics
Journal title
EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
ISSN journal
0014-2972 → ACNP
Volume
30
Issue
2
Year of publication
2000
Pages
162 - 166
Database
ISI
SICI code
0014-2972(200002)30:2<162:HIWATA>2.0.ZU;2-4
Abstract
Background Hydroxyurea is believed to inhibit human immunodeficiency virus type 1 (HIV-1) in HIV disease by decreasing the amount of intracellular deo xynucleotides needed for viral replication. A plasma concentration of 400 m u mol L-1 is tolerated in oncological diseases. The present study focused o n the possible interference of hydroxyurea with antigen-dependent T-cell ac tivation as an alternative explanation for inhibiting HIV replication in vi vo. Methods The effect of hydroxyurea on common antigen-induced cell proliferat ion was studied in peripheral blood mononuclear cells (PBMC) in vitro. Results Hydroxyurea inhibited Candida albicans-induced cell proliferation a t a low concentration (1 mu mol L-1), while at least 10 mu mol L-1 was requ ired to block HIV-1 replication in phytohaemagglutinin (PHA)-stimulated PBM C. Conclusion Hydroxyurea inhibits antigen-induced lymphoproliferation in vitr o at a concentration at which it does not inhibit PHA-induced HIV replicati on. Hydroxyurea may inhibit HIV-1 in CD4(+) T cells in vivo not only by dec reasing 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.