INVESTIGADORES
VIGLIANO Carlos
congresos y reuniones científicas
Título:
IN VITRO TREATMENT WITH ALLOPURINOL DECREASES IFN-GAMMA, IL-2 AND INTRACELULAR REACTIVE OXYGEN SPECIES PRODUCTIN IN PBMC FROM CHRONICALLY TRYPANOSOMA CRUZI-INFECTED SUBJECTS
Autor/es:
PEREZ-MAZLIAH D; ALVAREZ MG; VIGLIANO CA; PETTI M; ASHLEY H; ALBAREDA MC; TARLETON RL; VIOTTI R; LAUCELLA S
Lugar:
Atlanta
Reunión:
Congreso; American Society of Tropical Medicine and Hygiene. 59th Annual Meeting; 2010
Institución organizadora:
American Society of Tropical Medicine and Hygiene
Resumen:
Trypanosoma cruzi, the causative agent of Chagas
disease, is a protozoan parasite that affects 24 million people from Southern
California to Central and South America. We have recently evaluated T cell
responses after a sequential treatment with allopurinol followed by
benznidazole in subjects chronically infected with T. cruzi, and found that
total naïve (CD45RA+CCR7+CD62L+) and central memory (CD45RA-CCR7+CD62L+) CD4+
and CD8+ T cells, which are diminished in chronically infected subjects, significantly
increased after treatment with allopurinol, and these levels were generally
maintained at 24 months following combined sequential treatment. It is known
that allopurinol exerts anti-inflammatory effects and presents intrinsic free
radical scavenging ability. In the present study, we aimed to determine whether
the increase in total naïve and central memory T cells might be due to a direct
action of allopurinol on T cells. IFN-gamma and IL-2 ELISPOT responses to a T.
cruzi-derived amastigote lysate preparation decreased (2 to 7 fold) after in
vitro treatment of PBMC from chronically infected subjects with allopurinol
(300μg/ml). Both
baseline and PMA-induced production of intracellular reactive oxygen species in
T cells were diminished by in vitro treatment with allopurinol, thus
demonstrating a direct effect of allopurinol on T cells. Neither allopurinol in
a range concentration of 25-300μg/ml diluted in 0.01 M NaOH nor NaOH alone affected
CD4 and CD8 expression in human PBMC. Altogether, these findings support the
idea that, in addition to its trypanocidal activity, allopurinol could
attenuate the chronic activation of the host immune system.