IL-6 RELEASE AFTER INTESTINAL ISCHEMIA REPERFUSION IN RATS IS UNDER PARTIAL CONTROL OF TNF/

Although there is much evidence to substantiate the view that tumor ne crosis factor (TNF) plays a pivotal role in the pathogenesis of multip le organ injury subsequent to intestinal ischemia/reperfusion (I/R), i t is still unclear whether TNF is involved in triggering the release o f other inflammatory mediators in this condition. The current study wa s designed to determine the potential effects of TNF blockade, by mean s of monoclonal antibody (TNF MoAb) treatment, on plasma interleukin 6 (IL-6) in rats after acute intestinal I/R injury, Anesthetized rats u nderwent 75-min occlusion of superior mesenteric artery followed by 6 hr of reperfusion. The animals were treated with TNF MoAb or control p rotein at a dose of 20 mg/kg iv 30 min before the onset of I/R. Simila r IL-6 responses in both the portal and the systemic circulation were observed in animals subjected to intestinal I/R, who showed a progress ive increase in plasma IL-6 concentration upon release of the clamp. I n animals receiving TNF MoAb before I/R, the subsequent IL-6 release f ollowing reperfusion was significantly blunted compared to the levels in controls (P < 0.05). The present study demonstrates that the activa tion and/or release of IL-6 in the setting of acute gut I/R may, at le ast in part, be mediated via TNF-dependent mechanisms, providing furth er evidence that a complex interaction exists between TNF and IL-6. (C ) 1997 Academic Press.