Effects of hydroxyurea on malaria, parasite growth and adhesion in experimental models.
We recently raised concern over using hydroxyurea (HU) in the treatment of sickle cell disease in areas endemic for malaria, becauseit up-regulates the endothelial surface expression of ICAM-1, a major receptor for Plasmodium falciparum-infected erythrocytes in the brain. Using human in vitro models of cerebral malaria, we evaluated the interaction of HU with parasites and demonstrated that HU pretreatment increased the number of infected red blood cells adhering to the endothelium, but did not increase endothelial apoptosis. Moreover, using an experimental cerebral malaria model, HU pretreatment was found to prevent significantly mice from developing neurological syndrome by inhibiting parasite growth, opening potential therapeutic avenues.
Pino
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P
INSERM U511, Immunobiologie Cellulaire et Moléculaire des Infections Parasitaires, Faculté de Médecine Pitié Salpêtrière, Université Pierre et Marie Curie, 75013 Paris, France.
Taoufiq
Z
Z
Brun
M
M
Tefit
M
M
Franetich
J F
JF
Ciceron
L
L
Krishnamoorthy
R
R
Mazier
D
D
D000755:Anemia, Sickle Cell / Q000188:drug therapy; D000818:Animals; D000986:Antisickling Agents / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis; D002448:Cell Adhesion / Q000187:drug effects*; D042783:Endothelial Cells / Q000187:drug effects / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D004912:Erythrocytes / Q000378:metabolism / Q000469:parasitology; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D016779:Malaria, Cerebral / Q000188:drug therapy* / Q000401:mortality / Q000469:parasitology; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000401:mortality / Q000469:parasitology; D051379:Mice; D008810:Mice, Inbred C57BL; D010963:Plasmodium falciparum / Q000187:drug effects / Q000254:growth & development* / Q000502:physiology; D016896:Treatment Outcome
D000986:Antisickling Agents; D018799:Intercellular Adhesion Molecule-1; D006918:Hydroxyurea