Consequences of the Lack of IL-10 in Different Endotoxin Effects and its Relationship with Glucocorticoids

TODERO, MARÍA FLORENCIA; DANIELA, MONTAGNA; BARRIENTOS, GABRIELA; REARTE, BÁRBARA; FONTANALS, ADRIANA; YOKOBORI, NOEMÍ; TOBLLI, JORGE E.; FONTANALS, ADRIANA; YOKOBORI, NOEMÍ; TOBLLI, JORGE E.; CÓRDOBA-MORENO, MARLINA O.; PINEDA, GONZALO; RAMOS, MARÍA VICTORIA; ISTURIZ, MARTÍN A.; CÓRDOBA-MORENO, MARLINA O.; PINEDA, GONZALO; RAMOS, MARÍA VICTORIA; ISTURIZ, MARTÍN A.; TODERO, MARÍA FLORENCIA; DANIELA, MONTAGNA; BARRIENTOS, GABRIELA; REARTE, BÁRBARA

SHOCK

LIPPINCOTT WILLIAMS & WILKINS

Lugar: Philadelphia; Año: 2018 vol. 52 p. 264 - 273

1073-2322

Sepsis constitutes one of the major causes of death in intensive care units. In sepsis induced by Gram negative, while LPS initially induces an exacerbated secretion of proinflammatory cytokines leading to endotoxic shock and death resembling a septic shock, it is also capable of inducing refractoriness to subsequent challenge with LPS, a state known as endotoxin tolerance, which is considered the initial step of the immunosuppression found in septic patients. Since we previously demonstrated the importance of glucocorticoids in endotoxin tolerance, the aim of this study was to evaluate the contribution of IL-10 both in the endotoxic shock and in the development of the tolerance and its relationship with glucocorticoids. Our results show that, upon LPS challenge, IL-10 KO mice had an enhanced LPS sensitivity, along with elevated levels of proinflammatory cytokines as TNF-α, IL-12 and IFN-γ, and enhanced tissue damage, despite the high levels of glucocorticoids. This effect may be due, in part, to the higher expression of TNFRs in IL-10 KO mice. Further, the injection of dexamethasone did not protect IL-10 KO mice from a LPS lethal challenge. While tolerance was achieved in the absence of IL-10, it was weaker and the elevated levels of glucocorticoids were not able to reverse the high sensitivity of IL-10 KO mice to LPS. Nevertheless, glucocorticoids would play a pivotal role in the establishment and maintenance of this partial tolerance in IL-10KO mice. Finally, our results show that IL-10 and glucocorticoids could act in a bidirectional way influencing the inflammatory and anti-inflammatory periods.