Mifepristone (RU486) restores the humoral immune response in bacterial endotoxins-induced immunosuppressed mice

B. REARTE; A. MAGLIOCO; L. BALBOA; G. FERNANDEZ; M.ISTURIZ

Viña del Mar, Chile

Congreso; 9th Latin American Congress of Immunology, Viña del Mar, Chile November 3 – 7th 2009; 2009

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 demonstrate 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 LPS-induced immunosuppressed mice. Methods: BALB/c mice were immunosuppressed with LPS and then were treated with RU486 and immunized with sheep red blood cells.  Parameters of immunosuppression and immune response were evaluated by flow citometry and hemagglutination on day 7. Results: splenocytes CD11b+ of immunosuppressed mice showed a decreased MHC-II and TLR4 expression (control: MHCII = 317±28; TLR4= 16±2 vs immunosuppresed: MHCII=153±16; TLR4= 6±1; MFI±SEM, p<0.05). Moreover, immunosuppressed mice showed a reduced phagocytic capacity (control: 21±3 vs immunosuppressed: 11±1; % positive cell±SEM, p<0.05). Though the treatment with RU486 did not restore these parameters, a partial restoration in the humoral imune response was observed (immunosuppresed=3.5±0.9% vs immunosuppressed+RU486=26.3±6%; mean ±SEM %control p<0.01). Conclusion: RU486 partially restores the humoral immune response mediated by IgM and IgG antibodies in immunosuppressed mice and, eventually, would be a tool for the development of strategies to reinstall the immune response in late sepsis.