INTERLEUKIN-10 REDUCES THE SYSTEMIC INFLAMMATORY RESPONSE IN A MURINEMODEL OF INTESTINAL ISCHEMIA REPERFUSION/

Background. Intestinal ischemia/reperfusion (I/R) is known to increase systemic cytokine levels, as well as to activate neutrophils in dista nt organs. This study was designed to investigate the effect of interl eukin-10 (IL-10) on cytokine release, pulmonary neutrophil accumulatio n, and histologic changes in a murine model of I/R. Methods. Forty fem ale Swiss-Webster mice were divided into four groups. Group 1 underwen t 45 minutes of superior mesenteric artery occlusion followed by 3-hou r reperfusion (I/R). Group 2 underwent laparotomy alone (Sham). Group 3 underwent I/R, but was treated with IL-10, 10,000 units IP every 2 h ours, starting 1 hour before reperfusion (Pretreatment), Group 4 was t reated with an equal dose of IL-10, starting 1 hour after reperfusion (Posttreatment). All animals were killed at 3 hours, standard assays w ere performed for serum cytokine levels, and lung myeloperoxidase acti vity and intestinal histology were scored. Results. Serum cytokines (T NF-alpha and IL-6), lung myeloperoxidase levels, and histologic score were significantly reduced when IL-10 was administered either before o r after reperfusion. Conclusions. IL-10 reduced the severity of local and systemic inflammation in a murine model of intestinal I/R when giv en before or after reperfusion injury. These observations suggest that IL-10 may exert its effect by blocking cytokine production and distan t organ neutrophil accumulation.