INVESTIGADORES
CHIARELLA Paula
artículos
Título:
Mifepristone (RU486) restores humoral and T cell-mediated immune response in endotoxin immunosuppressed mice
Autor/es:
BÁRBARA REARTE; ANDREA MAGLIOCO; LUCIANA BALBOA; JUAN BRUZZO; VERÓNICA I. LANDONI; EVANGELINA LABORDE; PAULA CHIARELLA; RUGGIERO RAUL; GABRIELA C. FERNÁNDEZ; MARTÍN A. ISTURIZ
Revista:
CLINICAL AND EXPERIMENTAL IMMUNOLOGY
Editorial:
WILEY-BLACKWELL PUBLISHING, INC
Referencias:
Año: 2010 p. 568 - 577
ISSN:
0009-9104
Resumen:
Sepsis and septic shock can be caused by Gram-positive and -negative bacteria
and other microorganisms. In the case of Gram-negative bacteria, endotoxin,
a normal constituent of the bacterial wall, also known as lipopolysaccharide
(LPS), has been considered as one of the principal agents causing the undesirable
effects in this critical illness. The response to LPS involves a rapid
secretion of proinflammatory cytokines such as tumour necrosis factor
(TNF)-a, interleukin (IL)-1, IL-6, interferon (IFN)-g and the concomitant
induction of anti-inflammatory mediators such as IL-10, transforming
growth factor (TGF)-b or glucocorticoids, which render the host temporarily
refractory to subsequent lethal doses of LPS challenge in a process known as
LPS or endotoxin tolerance. Although protective from the development of
sepsis or systemic inflammation, endotoxin tolerance has also been pointed
out as the main cause of the non-specific humoral and cellular immunosuppression
described in these patients. In this report we demonstrate, using a
mouse model, that mifepristone (RU486), a known glucocorticoid receptor
antagonist, could play an important role in the restoration of both adaptive
humoral and cellular immune response in LPS immunosuppressed mice, suggesting
the involvement of endogenous glucocorticoids in this phenomenon.
On the other hand, using cyclophosphamide and gemcitabine, we
demonstrated that regulatory/suppressor CD4+CD25+forkhead boxP3+ and
GR-1+CD11b+ cells do not play a major role in the establishment or the
maintenance of endotoxin tolerance, a central mechanism for inducing an
immunosuppression state.