Secondary infections due to post-sepsis immunosuppression are a major cause of death in patients with sepsis. Strategies aimed at restoring immune functions offer a new perspective in the treatment of sepsis. In the present study, we used LPS (lipopolysaccharide)-immunosuppressed mice to analyse the effects of ATRA (all-trans retinoic acid) on different immune parameters. The IS (immunocompromised) group had decreased lymphocyte and increased MDSC (myeloid-derived suppressor cell) counts in lymph nodes. They also had an impaired in vitro T-cell proliferation, mediated by MDSCs. ATRA administration restored T-cell proliferation, which was associated with a decreased number of live MDSCs. The IS group treated with ATRA had an increased number of CD4+ and CD8+ T-cells. ATRA partially improved the primary humoral immune response, even when immunosuppression was established first and ATRA was administered subsequently. Our results demonstrate that ATRA restores immunocompetence by modulating the number of leucocytes and the survival of MDSCs, and thus represents an additional potential strategy in the treatment of the immunosuppressive state of sepsis.
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March 2014
Research Article|
November 01 2013
all-trans-Retinoic acid improves immunocompetence in a murine model of lipopolysaccharide-induced immunosuppression
Daiana Martire-Greco
;
*Laboratorio de Fisiología de los Procesos Inflamatorios, Instituto de Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Academia Nacional de Medicina, Pacheco de Melo 3081, C1425AUM, Buenos Aires, Argentina
Correspondence: Dr Daiana Martire-Greco (email daianamartire@hotmail.com).
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Veronica I. Landoni
;
Veronica I. Landoni
*Laboratorio de Fisiología de los Procesos Inflamatorios, Instituto de Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Academia Nacional de Medicina, Pacheco de Melo 3081, C1425AUM, Buenos Aires, Argentina
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Paula Chiarella
;
Paula Chiarella
†Laboratorio de Oncologia Experimental, Instituto de Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Academia Nacional de Medicina, Pacheco de Melo 3081, C1425AUM, Buenos Aires, Argentina
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Nahuel Rodriguez-Rodrigues
;
Nahuel Rodriguez-Rodrigues
*Laboratorio de Fisiología de los Procesos Inflamatorios, Instituto de Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Academia Nacional de Medicina, Pacheco de Melo 3081, C1425AUM, Buenos Aires, Argentina
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Pablo Schierloh
;
Pablo Schierloh
‡Laboratorio de Inmunologia de Enfermedades Respiratorias, Instituto de Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Academia Nacional de Medicina, Pacheco de Melo 3081, C1425AUM, Buenos Aires, Argentina
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Barbara Rearte
;
Barbara Rearte
*Laboratorio de Fisiología de los Procesos Inflamatorios, Instituto de Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Academia Nacional de Medicina, Pacheco de Melo 3081, C1425AUM, Buenos Aires, Argentina
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Martin A. Isturiz
;
Martin A. Isturiz
*Laboratorio de Fisiología de los Procesos Inflamatorios, Instituto de Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Academia Nacional de Medicina, Pacheco de Melo 3081, C1425AUM, Buenos Aires, Argentina
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Gabriela C. Fernandez
Gabriela C. Fernandez
*Laboratorio de Fisiología de los Procesos Inflamatorios, Instituto de Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Academia Nacional de Medicina, Pacheco de Melo 3081, C1425AUM, Buenos Aires, Argentina
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Clin Sci (Lond) (2014) 126 (5): 355–365.
Article history
Received:
May 14 2013
Revision Received:
September 16 2013
Accepted:
September 20 2013
Accepted Manuscript online:
September 20 2013
Citation
Daiana Martire-Greco, Veronica I. Landoni, Paula Chiarella, Nahuel Rodriguez-Rodrigues, Pablo Schierloh, Barbara Rearte, Martin A. Isturiz, Gabriela C. Fernandez; all-trans-Retinoic acid improves immunocompetence in a murine model of lipopolysaccharide-induced immunosuppression. Clin Sci (Lond) 1 March 2014; 126 (5): 355–365. doi: https://doi.org/10.1042/CS20130236
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