Interleukin-2 vermindert die hepatische Schädigung nach isolierter Ischämie des Darmes

Abstract

Introduction: Intestinal ischemia/reperfusion (IR) results in tissue destruction in the gut, but may also induce oxidative stress and cellular damage in distant organs, such as the liver. It remains unclear whether inhibition or stimulation of the inflammatory response may help to reduce tissue destruction after IR. Therefore, the effects of pro- and anti-inflammatory cytokines on oxidative stress and tissue destruction in the intestine and liver after intestinal IR were analyzed. Methods: Male Lewis rats underwent 60 min of intestinal ischemia by clamping of the superior mesenteric artery or were sham operated. Animals received an IV bolus of 40 µg/kg IL-2, IL-10 or vehicle before reperfusion. At 20 min 1 h, 4 h, and 24 h after reperfusion animals were sacrificed and blood and tissue samples were obtained for analysis of serum levels of NO- 2/NO- 3, hyaluronic acid (HA), transaminases (AST), and tissue GSH levels, as well as for RT-PCR of the inducible nitric oxide synthase (NOS-2) and hemeoxygenase-1 (HO-1) mRNA. Results: IR resulted in tissue destruction and oxidative stress in both organs indicated by elevated HA and AST serum levels and significantly reduced GSH tissue levels. Concomitantly increased expression of NOS- 2 and HO-1 mRNA was detectable in liver and intestine after IR. IL-2 administration resulted in diminished hepatic tissue destruction despite sustained reduction of GSH. IL-2 further increased NOS-2 and HO-1 mRNA expression in both organs after IR. In contrast, IL-10 resulted in increased tissue damage, but failed to increase NOS-2 or HO-1 mRNA expression in the small intestine or liver after IR. Discussion: Intestinal IR does not only result in oxidative stress in the intestine but elicits also oxidative stress in the liver. The beneficial effect of IL-2 was not due to reduction of oxidative stress, but rather due to increased expression of NOS-2 and HO-1 mRNA. In contrast, IL-10 which failed to increase NOS-2 and HO-1 mRNA expression in both organs led to increased tissue destruction after IR. Conclusions: Tissue destruction and oxidative stress in intestinal IR are not limited to the intestine. The beneficial effect of IL-2 on IR may be due to decreased neutrophil infiltration and enhanced neutralization of oxygen intermediates by nitric oxide in the intestine and liver.