DEHYDROEPIANDROSTERONE AND METYRAPONE PARTIALLY RESTORE THE ADAPTIVE HUMORAL AND CELLULAR IMMUNE RESPONSE IN ENDOTOXIN IMMUNOSUPPRESSED MICE.

REARTE, BÁRBARA; MAGLIOCO, ANDREA; MACHUCA, DAMIÁN; MARTIRE GRECO, DAIANA; LANDONI, VERÓNICA I.; RODRIGUEZ-RODRIGUES, NAHUEL; MEISS, ROBERTO; FERNÁNDEZ, GABRIELA C. ; ISTURIZ, MARTÍN A.

Congreso; LXI Reunión Anual de la Sociedad Argentina de Inmunología; 2013

SAI

The prior exposure to endotoxins i.e. lipopolysaccharides (LPS) renders the host temporarily refractory to subsequent LPS challenge (endotoxin tolerance). Clinically, this state has also been pointed out as the initial cause of the non-specific humoral and cellular immunosuppression described in late sepsis patients. We recently demonstrated the restoration of immune response with mifepristone, a receptor antagonist of glucocorticoids (GC) in LPS-induced immunosuppressed mice. The aim of this work was evaluate the treatment effect with other modulators of GC i.e. dehydroepiandrosterone (DHEA), a hormone with anti-GC properties, or metyrapone (MET) an inhibitor of GC synthesis, in an immunosuppression model. For this, mice were LPS immunosuppressed (IS), treated with the drugs and on the seventh day we evaluated different parameters of the immune response. These drugs were able to significantly restore the humoral immune response in IS mice (*p menor 0.05, IS versus Control (C); #p menor 0.05, IS-DHEA and IS-MET versus IS; mean(haemagglutination titre)±SEM). A significant recovery of proliferative responsiveness was also observed when splenocytes were obtained from DHEA- or MET-treated IS mice (*p menor 0.05, IS versus C; #p menor 0.05, IS-DHEA and IS-MET versus IS; mean(Δ cpm)±SEM). In addition, these treatments restored the delayed -type hypersensitivity response (DTH) in IS mice (*p menor 0.05, IS versus C; #p menor 0.05, IS-DHEA and IS-MET versus IS; mean(DTH reaction)±SEM). Finally, although neither DHEA nor MET improved the reduced CD4 lymphocyte count in spleen from IS mice, both treatments promoted splenic architecture reorganization, partially restoring the distinct cellular components and their localization in the spleen. The results from this study indicate that DHEA and MET could play an important role in the restoration of both adaptive humoral and cellular immune response in LPS immunosuppressed mice, reinforcing the concept of a central involvement of endogenous GC on this phenomenon.