Hypertonic preconditioning prevents hepatocellular injury following ischemia/reperfusion in mice: A role for interleukin 10

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Abstract
Ischemia/reperfusion (I/R) of the liver occurs in many clinical scenarios including trauma, elective surgery, and transplantation. Events initiated by this process can lead to inflammation in the liver, culminating in local injury as well as distant organ dysfunction. Recent studies have suggested that hypertonic saline exerts anti-inflammatory effects, which may be beneficial in preventing organ injury. In the present study, we examine the effect of hypertonic saline on the development of liver inflammation following I/R in both rat and mouse models. Hypertonic pretreatment was shown to prevent liver enzyme release concomitant with a reduction in liver neutrophil sequestration. Hypertonic saline appeared to exert this effect by inhibiting liver tumor necrosis factor α (TNF-α) generation, an effect that culminated in reduced liver adhesion molecule expression. Hypertonic saline pretreatment was shown to augment liver interleukin 10 (IL-10) expression following I/R, as a potential mechanism underlying its anti-inflammatory effect. To examine the role of IL-10 in the protective effect of hypertonic saline on liver I/R injury, we used a murine model of I/R. In wild type mice, hypertonic pretreatment similarly prevented liver injury induced by I/R. However, in IL-10 knockout animals, hypertonic pretreatment was unable to prevent the liver enzyme release, TNF-α generation, or neutrophil sequestration induced by I/R. In conclusion, these findings define a novel mechanism responsible for the anti-inflammatory effects of hypertonic saline and also suggest a potential clinical role for hyperosmolar solutions in the prevention of liver injury associated with I/R. Supplementary material for this article can be found on the Hepatology website (http://interscience.wiley.com/jpages/0270-9139/suppmat/index.html). (Hepatology 2004;40:211-220.)