In vitro treatment with allopurinol decreases IFN-g, IL-2 and intracellular reactive oxygen species production in PBMC from chronically Trypanosoma cruzi-infected subjects

PEREZ-MAZLIAH D; MARÍA G. ALVAREZ; CARLOS A. VIGLIANO; MARCOS PETTI; ASHLEY HARTLEY; MARÍA C. ALBAREDA; RICK L. TARLETON; VIOTTI R; LAUCELLA S

Atlanta

Congreso; 59 ASTMH Annual Meeting; 2010

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.