Allopurinol reduces antigen-specific and polyclonal activation of human T cells

Damián Pérez-Mazliah; María C Albareda; María G Alvarez; Bruno Lococo; Graciela L Bertocchi; Marcos Petti; Rodolfo J Viotti; Susana A Laucella

doi:10.3389/fimmu.2012.00295

Allopurinol reduces antigen-specific and polyclonal activation of human T cells

Damián Pérez-Mazliah, María C Albareda, María G Alvarez, Bruno Lococo, Graciela L Bertocchi, Marcos Petti, Rodolfo J Viotti, Susana A Laucella

The Hull York Medical School

Research output: Contribution to journal › Article › peer-review

Abstract

Allopurinol is the most popular commercially available xanthine oxidase inhibitor and it is widely used for treatment of symptomatic hyperuricaemia, or gout. Although, several anti-inflammatory actions of allopurinol have been demonstrated in vivo and in vitro, there have been few studies on the action of allopurinol on T cells. In the current study, we have assessed the effect of allopurinol on antigen-specific and mitogen-driven activation and cytokine production in human T cells. Allopurinol markedly decreased the frequency of IFN-γ and IL-2-producing T cells, either after polyclonal or antigen-specific stimulation with Herpes Simplex virus 1, Influenza (Flu) virus, tetanus toxoid and Trypanosoma cruzi-derived antigens. Allopurinol attenuated CD69 upregulation after CD3 and CD28 engagement and significantly reduced the levels of spontaneous and mitogen-induced intracellular reactive oxygen species in T cells. The diminished T cell activation and cytokine production in the presence of allopurinol support a direct action of allopurinol on human T cells, offering a potential pharmacological tool for the management of cell-mediated inflammatory diseases.

Original language	English
Pages (from-to)	295
Journal	Frontiers in immunology
Volume	3
DOIs	https://doi.org/10.3389/fimmu.2012.00295
Publication status	Published - 2012

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10.3389/fimmu.2012.00295

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title = "Allopurinol reduces antigen-specific and polyclonal activation of human T cells",

abstract = "Allopurinol is the most popular commercially available xanthine oxidase inhibitor and it is widely used for treatment of symptomatic hyperuricaemia, or gout. Although, several anti-inflammatory actions of allopurinol have been demonstrated in vivo and in vitro, there have been few studies on the action of allopurinol on T cells. In the current study, we have assessed the effect of allopurinol on antigen-specific and mitogen-driven activation and cytokine production in human T cells. Allopurinol markedly decreased the frequency of IFN-γ and IL-2-producing T cells, either after polyclonal or antigen-specific stimulation with Herpes Simplex virus 1, Influenza (Flu) virus, tetanus toxoid and Trypanosoma cruzi-derived antigens. Allopurinol attenuated CD69 upregulation after CD3 and CD28 engagement and significantly reduced the levels of spontaneous and mitogen-induced intracellular reactive oxygen species in T cells. The diminished T cell activation and cytokine production in the presence of allopurinol support a direct action of allopurinol on human T cells, offering a potential pharmacological tool for the management of cell-mediated inflammatory diseases.",

author = "Dami{\'a}n P{\'e}rez-Mazliah and Albareda, {Mar{\'i}a C} and Alvarez, {Mar{\'i}a G} and Bruno Lococo and Bertocchi, {Graciela L} and Marcos Petti and Viotti, {Rodolfo J} and Laucella, {Susana A}",

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doi = "10.3389/fimmu.2012.00295",

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T1 - Allopurinol reduces antigen-specific and polyclonal activation of human T cells

AU - Pérez-Mazliah, Damián

AU - Albareda, María C

AU - Alvarez, María G

AU - Lococo, Bruno

AU - Bertocchi, Graciela L

AU - Petti, Marcos

AU - Viotti, Rodolfo J

AU - Laucella, Susana A

PY - 2012

Y1 - 2012

N2 - Allopurinol is the most popular commercially available xanthine oxidase inhibitor and it is widely used for treatment of symptomatic hyperuricaemia, or gout. Although, several anti-inflammatory actions of allopurinol have been demonstrated in vivo and in vitro, there have been few studies on the action of allopurinol on T cells. In the current study, we have assessed the effect of allopurinol on antigen-specific and mitogen-driven activation and cytokine production in human T cells. Allopurinol markedly decreased the frequency of IFN-γ and IL-2-producing T cells, either after polyclonal or antigen-specific stimulation with Herpes Simplex virus 1, Influenza (Flu) virus, tetanus toxoid and Trypanosoma cruzi-derived antigens. Allopurinol attenuated CD69 upregulation after CD3 and CD28 engagement and significantly reduced the levels of spontaneous and mitogen-induced intracellular reactive oxygen species in T cells. The diminished T cell activation and cytokine production in the presence of allopurinol support a direct action of allopurinol on human T cells, offering a potential pharmacological tool for the management of cell-mediated inflammatory diseases.

AB - Allopurinol is the most popular commercially available xanthine oxidase inhibitor and it is widely used for treatment of symptomatic hyperuricaemia, or gout. Although, several anti-inflammatory actions of allopurinol have been demonstrated in vivo and in vitro, there have been few studies on the action of allopurinol on T cells. In the current study, we have assessed the effect of allopurinol on antigen-specific and mitogen-driven activation and cytokine production in human T cells. Allopurinol markedly decreased the frequency of IFN-γ and IL-2-producing T cells, either after polyclonal or antigen-specific stimulation with Herpes Simplex virus 1, Influenza (Flu) virus, tetanus toxoid and Trypanosoma cruzi-derived antigens. Allopurinol attenuated CD69 upregulation after CD3 and CD28 engagement and significantly reduced the levels of spontaneous and mitogen-induced intracellular reactive oxygen species in T cells. The diminished T cell activation and cytokine production in the presence of allopurinol support a direct action of allopurinol on human T cells, offering a potential pharmacological tool for the management of cell-mediated inflammatory diseases.

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