CONICET | Buscador de Institutos y Recursos Humanos

Abstract: Introduction: Endotoxin tolerance, defined as a reduced responsiveness to lipopolysaccharide (LPS) after a first encounter with endotoxin, could be involved in sepsis-associated immunosuppression. Previously we demonstrated that RU486, a glucocorticoid-receptor antagonist, induces the disruption of tolerance in mice. Objective: The aim of this study was to evaluate the effect of RU486 on immune response in endotoxin tolerant mice. BALB/c mice were tolerized with LPS, treated with RU486 and immunized with sheep red blood cells (sRBC). Parameters of immunosuppression and humoral immune response were evaluated by flow citometry and hemagglutination on day 7. To evaluate cellular immune response, tolerant mice were treated with RU486 and inoculated with radiated tumor cells and then were challenged with live tumor cells. Tumor presence was observed ten days later. Results: Tolerant mice splenocytes showed decreased MHCII and TLR4 expression (control: MHCII= 317±28; TLR4= 2.6±0.1 vs tolerant: MHCII=153±16; TLR4= 1.5±0.08; MFI±SEM, p<0.05) and a reduced specific proliferative response against sRBC (control: 7365±736 vs tolerant: 77± 70; mean ±SEM).Though the treatment with RU486 did not restore these parameters, a partial recovery of the humoral immune response was observed (tolerant: 3.5±0.9% vs tolerant+RU486: 26.3±6%; mean ±SEM %control p<0.01). RU486 treatment also restored the cellular immune response in tolerant mice (tumor frequency = tolerant: 10/11; tolerant+RU486: 3/12).Conclusion: RU486 partially restores the humoral immune response mediated by IgM and IgG as well as cellular immune response in tolerant mice. This eventually would be a tool for the development of strategies to reinstall the immune response in late sepsis.