THE IL-10 PARTICIPATION IN THE INDUCED-ENDOTOXINS BACTERIAL TOLERANCE/IMMUNOSUPPRESSION

CÓRDOBA MORENO, MARLINA ; FONTANALS, ADRIANA; MAGLIOCO, ANDREA; MARTIRE GRECO D; RODRIGUEZ-RODRIGUES, NAHUEL; LANDONI VERÓNICA INÈS; FERNANDEZ G.C; ISTURIZ M.A; REARTE B

Congreso; Inmunocolombia; 2015

Septic processes constitute one of the major causes of death in intensive care units reaching a mortality rate of 30% in Europe as well as in countries such as the US. Even though sepsis presents asimultaneous induction of both an inflammatory and anti-inflammatory response, in early phases predominates a hyper-inflammatory state whereas during later phases an anti-inflammatory responsebecomes predominant. It is during this last state that more than 70% of sepsis deaths occur due to failure in controlling pathogens associated to an immunosuppression state. Treatments in sepsis havebeen done in the last 30 years using anti-inflammatory agents, a procedure that universally failed. In Sepsis caused by Gram-negative bacteria, endotoxins, a normal constituent of the bacterial outer wall,also known as lipopolysaccharide (LPS), has been considered one of the principal agents causing the undesirable effects in this critical illness. The response to LPS involves a rapid secretion of bothmediators proinflammatory as well as anti-inflammatory. Exposure of the host to repeated LPS dose induces a state of hyporesponsiveness to subsequent simulations, in a process known as LPS orendotoxins 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. By using a mousemodel of LPS-induced tolerance / immunosuppression, we recently demonstrated that the endogenous glucocorticoids seem to be central molecules in the management of cellular and humoralimmunosuppression induced by LPS in murine models, since different drugs with anti-glucocorticoids activity (RU486, DHEA, Metyrapone) revert this immunosuppression state. However, also othersmediators have been proposed as causative factors of immunosuppression in sepsis such as anti-inflammatory cytokines (e.g.IL-10 and TGF-beta). In recent years it has been determined to IL-10 asresponsible agent for the immunosuppression and the high levels observed during late sepsis it has been associated with a worse prognosis. Taking into account that our central objective is to sek strategiesdirected to reverse the immunosuppression, the aim of this work was to evaluate the contribution of IL-10 in the establishment of the immunosuppression induced by LPS in a murine model and its potentialrelationship with glucocorticoids. Thus, we evaluated different aspects from the tolerance/immunosuppression phenomena induced by LPS using Wild type (WT) and IL-10 deficient (KO) BALB/c mice.