Analysis of immune response patterns in naïve and Plasmodium berghei-infected young rats following a ferroquine treatment.
The direct antimalarial activity of ferroquine (FQ, SSR97193), a chloroquine (CQ) derivative, is well established. To determine whether the FQ anti-parasite activity affects the host immune properties, we have investigated its effect on several immunological parameters in young rats infected with Plasmodium berghei and compared it with that of CQ. In uninfected young rats, treatment with either drug did not show any impairment in the cellular distribution of spleen cells in their response to mitogens and did not induce the production of IL-10 in vivo. After infection, rats treated with CQ or FQ showed no parasitemia and survived with no recrudescence, in comparison with placebo. Nevertheless, FQ cured young rats more rapidly than its parent drug. Analysis of cellular distribution including CD4+TCR+, CD8+TCR+, NK and NKT cells in blood and spleen and the production of specific antibodies did not reveal any alteration of these parameters in infected young rats treated either with CQ or FQ. However, we observed a persistence of CD4+CD25+T-cells in infected CQ-treated rats when compared with infected FQ-treated rats, very likely related to the delay of blood parasite clearance by CQ-treatment. Another significant difference is that the CQ treatment dramatically inhibited the lymphoproliferative response of young infected rats when compared with FQ. Collectively, the absence of any observable immunotoxic effects due to FQ in naïve and infected young rats, together with previous results indicating the susceptibility to FQ of all Plasmodium falciparum field isolates and CQ-resistant strains make it a promising drug for malarial treatment.
Pierrot
Christine
C
Unité Inserm 547, IFR 17, Institut Pasteur de Lille, 1 rue du Prof. Calmette, 59019 Lille, France.
Lafitte
Sophia
S
Dive
Daniel
D
Fraisse
Laurent
L
Brocard
Jacques
J
Khalife
Jamal
J
D000634:Aminoquinolines / Q000627:therapeutic use*; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D000962:Antimalarials / Q000627:therapeutic use*; D049109:Cell Proliferation; D002478:Cells, Cultured; D002738:Chloroquine / Q000627:therapeutic use; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005296:Ferrous Compounds / Q000627:therapeutic use*; D005434:Flow Cytometry; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000097:blood; D008288:Malaria / Q000188:drug therapy / Q000276:immunology*; D000075163:Metallocenes; D010962:Plasmodium berghei; D051381:Rats; D011916:Rats, Inbred F344; D013154:Spleen / Q000276:immunology
D000634:Aminoquinolines; D000913:Antibodies, Protozoan; D000962:Antimalarials; D005296:Ferrous Compounds; D007074:Immunoglobulin G; D000075163:Metallocenes; D016753:Interleukin-10; D007371:Interferon-gamma; D002738:Chloroquine; C479230:ferroquine