The ability of chloroquine to prevent tat-induced cytokine secretion by monocytes is implicated in its in vivo anti-human immunodeficiency virus type 1 activity.
Hydroxychloroquine at 1 microM reduces the load of human immunodeficiency virus type 1 (HIV-1) in patients, whereas chloroquine (CQ) concentrations above 3 microM are required for inhibition of HIV-1 replication in peripheral blood mononuclear cells. Exogenous HIV-1 Tat reaches the cytosol of T cells by using low endosomal pH, and endosome neutralization by CQ prevents Tat from entering and affecting T cells. We show here that 0.6 microM CQ inhibits cytokine secretion induced by Tat in monocytes without affecting lipopolysaccharide-triggered cytokine release. This finding suggests that the in vivo anti-HIV-1 effect of CQ results not from a direct effect on the infected cell but rather from the capacity of CQ to prevent Tat from perturbing the cytokine balance.
UMR5539 CNRS, Département Biologie-Santé, Case 107, Université Montpellier II, 34095 Montpellier Cedex 05, France.
Fabienne
F
Rayne
Agnès
A
Vendeville
Anne
A
Bonhoure
Bruno
B
Beaumelle
D019380:Anti-HIV Agents / Q000494:pharmacology*; D002738:Chloroquine / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism*; D015696:Gene Products, tat / Q000037:antagonists & inhibitors*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D054322:tat Gene Products, Human Immunodeficiency Virus
D019380:Anti-HIV Agents; D016207:Cytokines; D015696:Gene Products, tat; D015850:Interleukin-6; D054322:tat Gene Products, Human Immunodeficiency Virus; D002738:Chloroquine