Effect of Glucocorticoids in the Development of Endotoxin Tolerance

BÁRBARA REARTE; VERÓNICA I. LANDONI; PAULA CHIARELLA; EVANGELINA LABORDE; MARÍA F. LÓPEZ; GABRIELA FERNANDEZ; MARTÍN A. ISTURIZ

Rio de Janeiro-Brasil

Congreso; 13th International Congress of Immunology; 2007

Systemic inflammatory phenomena, usually called SIRS (sepsis, hemorrhagic, traumatic shock, etc.), are consequence of the exposure to different stimuli that induce proinflammatory cytokines release. This situation is rapidly compensated by a sudden increase of antiinflammatory cytokines that frequently, conclude in an immunosuppression state. Sepsis is, perhaps, the most relevant SIRS and more of 50% of the sepsis are due to infections by gram negative bacteria. LPS, the outer membrane components of these bacteria, are the causal agents of the systemic proinflammatory phase, and could be involved in the immunosuppression state observed in late sepsis. LPS tolerance phenomenon, one of the most relevant events in sepsis, is defined by a host reduced capacity to produce proinflammatory cytokines after previous LPS exposure. The comprehension of mechanisms underlying the LPS tolerance phenomenon is very important since they could be involved in the immunosuppression observed in sepsis, which is one of the most important causes of high mortality in patients. The aim of this work was to study some aspects related to LPS tolerance involved-mechanisms. Thus, using in vivo and in vitro models we analyzed the effects of glucocorticoids and some cytokines in two different phases of this phenomenon. In the initial phase, or tolerance establishment, we evaluated the role of dexamethasone and TNF-+. In the second one, or tolerance maintenance, we studied the role of IFN-
and a competitive inhibitor of glucocorticoids actions, RU486.