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- Title
Immunomodulatory Role of Chloroquine and Pyrimethamine in Plasmodium yoelii 17XL Infected Mice.
- Authors
Ramos-Avila, A.; Ventura-Gallegos, J. L.; Zentella-Dehesa, A.; Machuca-Rodríguez, C.; Moreno-Altamirano, M. M.; Narváez, V.; Legorreta-Herrera, M.
- Abstract
Chloroquine (CLQ) and Pyrimethamine (PYR) are used for the treatment of malaria and some autoimmune diseases; although their mechanism of action is only partially understood, their therapeutic effectiveness in the second case has been attributed to their ability to increase apoptosis of T lymphocytes. In view of the potential for immunomodulation during malaria chemotherapy, we investigated the effects of CLQ and PYR treatment on lymphocyte apoptosis and cytokine expression during infection with blood-stage Plasmodium. This work shows that infection of BALB/ c mice with Plasmodium yoelii 17XL (Py17XL) reduced apoptosis in spleen cells but when infected mice were treated with CLQ, apoptosis of B and T lymphocytes increased significantly via a Fas-mRNA expression independent mechanism associated with downregulation of Bcl-2 expression, whereas treatment with PYR increased apoptosis to a lesser extent and only in B lymphocytes. CLQ treatment of Py17XL infected mice upregulated tumour necrosis factor- α mRNA expression, while PYR treatment increased interferon- γ mRNA expression. In infected mice, treatment with CLQ downregulated expression of the anti-inflammatory cytokines, interleukin-10 and transforming growth factor- β (TGF- β), while PYR treatment upregulated TGF- β. Thus, in addition to their anti-malarial effects, both drugs modulate the immune response in malaria by increasing apoptosis and modulating the mRNA expression of cytokines involved in parasite elimination and regulation of inflammatory responses.
- Subjects
ANTIMALARIALS; CHLOROQUINE; IMMUNOLOGIC diseases; ANTIBODY-directed enzyme prodrug therapy; PLASMODIUM yoelii; T cells; MALARIA
- Publication
Scandinavian Journal of Immunology, 2007, Vol 65, Issue 1, p54
- ISSN
0300-9475
- Publication type
Article
- DOI
10.1111/j.1365-3083.2006.01869.x