Effect of RU486 on cellular and humoral immune response in endotoxin tolerance model

REARTE BARBARA; ANDREA MAGLIOCO; LUCIANA BALBOA; YOKOBORI N; BRUZZO J; RAÚL A. RUGGIERO; GABRIELA FERNÁNDEZ; MARTÍN A. ISTURIZ

Congreso; 14th International Congress of immunology. Japón,; 2010

Abstract: Introduction: Endotoxin tolerance, defined as a reduced responsiveness to lipopolysaccharide (LPS) after a firstencounter with endotoxin, could be involved in sepsis-associated immunosuppression. Previously we demonstrated thatRU486, a glucocorticoid-receptor antagonist, induces the disruption of tolerance in mice. Objective: The aim of this study wasto 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 humoralimmune 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 tumorcells. Tumor presence was observed ten days later. Results: Tolerant mice splenocytes showed decreased MHCII and TLR4expression (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 thetreatment 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 cellularimmune response in tolerant mice (tumor frequency = tolerant: 10/11; tolerant+RU486: 3/12).Conclusion: RU486 partiallyrestores the humoral immune response mediated by IgM and IgG as well as cellular immune response in tolerant mice. Thiseventually would be a tool for the development of strategies to reinstall the immune response in late sepsis.