Multiple organ inflammatory response to portosystemic shunt in the rat

Abstract

Portosystemic shunt surgery is the best procedure to prevent recurrent bleeding of esophageal varices, but carries a high risk of postoperative inflammatory complications, including hepatic encephalopathy. Thus, portosystemic shunting procedures could induce a systemic inflammatory response with multiple organ dysfunction syndrome, including hepatic encephalopathy. To verify this hypothesis we used male Wistar rats at 6weeks of postoperative evolution: Control (CR; n=14), Sham-operated (SO; n=8) and rats with end-to-side portacaval shunt (PCS; n=15). TNF-α, IL-1β and IL-10 were assayed by ELISA techniques, the expression of the endothelial constitutive nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), constitutive and inducible heme-oxygenase (HO-1 and HO-2) were assayed by Western-blot. mRNA levels of HO-1, HO-2, TNF-α, IL-1β and IL-10 were quantified by reverse transcriptase polymerase chain reaction amplification (RT-PCR) in the small bowel, liver, spleen and lungs. Portacaval shunting in the rat produces an interorgan imbalance of pro- and anti-inflammatory mediators. TNF-α mRNA expression is decreased in the liver (0.69±0.28, p<0.05). The hepatic production of IL-Iβ (204.13±71.90pg/100g; p<0.001) and IL-10 (4505.47±337.97pg/100g; p<0.001) is also decreased. However, the intestinal pro-inflammatory (TNF-α: 1471.86±153.62pg/100g, p<0.001; IL-1β: 48.35±9.84pg/100g, p<0.001 and iNOS: 0.59±0.01, p<0.01) and anti-inflammatory (IL-10: 1503.39±53.5pg/100g, p<0.001 and HO-1: 2.23±0.16, p<0.001) mediators are increased. Total portacaval shunting in the rat induces impairments of pro- and anti-inflammatory mediators in the splanchnic–lung axis that could be associated with a multiple organ dysfunction syndrome. Therefore, the complications after portosystemic shunts could be integrated into a systemic inflammatory response of possible intestinal origin.