all-trans-retinoic acid improves immunocompetence in a murine model of lipopolysaccharide-induced immunosuppression.
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.
*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.
Daiana
D
Martire-Greco
Veronica I
VI
Landoni
Paula
P
Chiarella
Nahuel
N
Rodriguez-Rodrigues
Pablo
P
Schierloh
Barbara
B
Rearte
Martin A
MA
Isturiz
Gabriela C
GC
Fernandez
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D005434:Flow Cytometry; D007121:Immunocompetence / Q000187:drug effects*; D007165:Immunosuppression Therapy; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D014212:Tretinoin / Q000494:pharmacology*
D008070:Lipopolysaccharides; D014212:Tretinoin