IMMUNOLOGICAL CHANGES IN IL-10-DEFICIENT MICE DURING THE COURSE OF IMMUNOSUPPRESSION INDUCED BY BACTERIAL ENDOTOXINS

CORDOBA MORENO MARLINA; FONTANALS ADRIANA; MARTIRE GRECO DAIANA; FERNÁNDEZ GABRIELA CRISTINA; ISTURIZ MARTIN AMADEO; RAMOS VICTORIA; REARTE BARBARA

Buenos Aires

Congreso; IV LASID Meeting, LXII Argentinean Immunology Society Meeting, II French Argentinean Immunology meeting; 2015

Septic processes constitute one of the major causes of death in intensive care units reaching a mortality rate of 30% in Europe and the United States. Even though sepsis presents a simultaneous induction of both a pro-inflammatory and anti-inflammatory response, the predominant clinical status varies over time. In Sepsis caused by Gram-negative bacteria, endotoxins, also known as lipopolysaccharide (LPS), induces a state ofhyporesponsiveness known as LPS or endotoxins tolerance. Clinically, this state has been pointed out as one of initial causes of the immunosuppression described in late sepsis patients. We previously demonstrated the glucocorticoids participation in this immunosuppression. However, others mediators have also been proposed as causative factors of immunosuppression in sepsis such as anti-inflammatory cytokines as IL-10. It recently has been determined as responsible agent the immunosuppression due to that were found high levels during late sepsis which was associated with a worse prognosis.The deficient IL-10 (KO) mice showed an augmented sensitivity to a LPS challenge, which was reflected in the high and sustained over time levels of different proinflammatory cytokines particularly the TNF alfa, and probably to the high levels on TNF-R. These results indicate that IL-10 is involved in early events of the encounter with endotoxin to prevent an exacerbated inflammatory response and avoided thereby death. However, reducing the initial inflammation even in the absence of IL-10, it was possible to establish a tolerance and immunosuppression state similar to that observed in WT mice. In addition, the absence of IL-10 induced a substantial increase of the secondary immune response in basal conditions. Furthermore, we observed that Dexamethasone (dexa) treatment induced a partial protection in KO mice, suggesting that the refractory effect of dexa could be manifested fully only in presence of IL-10. However, the partial effect together with the increase in levels of endogenous corticosterone both in KO basal and KO tolerant mice, propose an important role for the glucocorticoids in conditions in which IL-10 is absent, exerting a regulatory effect on TNF alfa levels, thus avoiding lethality of endotoxin. These facts should be further developed in the future.