PMID- 17212767
OWN - NLM
STAT- MEDLINE
DCOM- 20070220
LR  - 20131121
IS  - 0300-9475 (Print)
IS  - 0300-9475 (Linking)
VI  - 65
IP  - 1
DP  - 2007 Jan
TI  - Immunomodulatory role of chloroquine and pyrimethamine in Plasmodium yoelii 17XL 
      infected mice.
PG  - 54-62
AB  - 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-alpha mRNA 
      expression, while PYR treatment increased interferon-gamma mRNA expression. In 
      infected mice, treatment with CLQ downregulated expression of the 
      anti-inflammatory cytokines, interleukin-10 and transforming growth factor-beta 
      (TGF-beta), while PYR treatment upregulated TGF-beta. 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.
FAU - Ramos-Avila, A
AU  - Ramos-Avila A
AD  - Laboratorio de Inmunologia Molecular, Facultad de Estudios Superiores Zaragoza, 
      Universidad Nacional Autonoma de Mexico, Mexico D.F.
FAU - Ventura-Gallegos, J L
AU  - Ventura-Gallegos JL
FAU - Zentella-Dehesa, A
AU  - Zentella-Dehesa A
FAU - Machuca-Rodriguez, C
AU  - Machuca-Rodriguez C
FAU - Moreno-Altamirano, M M
AU  - Moreno-Altamirano MM
FAU - Narvaez, V
AU  - Narvaez V
FAU - Legorreta-Herrera, M
AU  - Legorreta-Herrera M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Scand J Immunol
JT  - Scandinavian journal of immunology
JID - 0323767
RN  - 0 (Cytokines)
RN  - 0 (Immunologic Factors)
RN  - 0 (RNA, Messenger)
RN  - 0 (Reactive Oxygen Species)
RN  - 886U3H6UFF (Chloroquine)
RN  - Z3614QOX8W (Pyrimethamine)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Chloroquine/*pharmacology
MH  - Cytokines/genetics
MH  - Immunologic Factors/*pharmacology
MH  - Malaria/*drug therapy/immunology/metabolism
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - *Plasmodium yoelii
MH  - Pyrimethamine/*pharmacology
MH  - RNA, Messenger/analysis
MH  - Reactive Oxygen Species/metabolism
EDAT- 2007/01/11 09:00
MHDA- 2007/02/21 09:00
CRDT- 2007/01/11 09:00
PHST- 2007/01/11 09:00 [pubmed]
PHST- 2007/02/21 09:00 [medline]
PHST- 2007/01/11 09:00 [entrez]
AID - SJI1869 [pii]
AID - 10.1111/j.1365-3083.2006.01869.x [doi]
PST - ppublish
SO  - Scand J Immunol. 2007 Jan;65(1):54-62. doi: 10.1111/j.1365-3083.2006.01869.x.