EXOGENOUSLY ADMINISTERED INTERLEUKIN-10 DECREASES PULMONARY NEUTROPHIL INFILTRATION IN A TUMOR NECROSIS FACTOR-DEPENDENT MURINE MODEL OF ACUTE VISCERAL ISCHEMIA

Introduction: Visceral ischemia and reperfusion associated with thorac oabdominal aortic aneurysm (TAAA) repair results in lung injury, which appears to be mediated in part by proinflammatory cytokines. The purp ose of this study was to determine the effect of exogenous administrat ion of the antiinflammatory cytokine, recombinant human IL-10 (rhIL-10 ), on proinflammatory cytokine production (IL-6 and TNF alpha) and pul monary neutrophil infiltration after acute visceral ischemia-reperfusi on. Methods: Two hours before 25 minutes of supraceliac aortic occlusi on, 80 C57BL/6 mice (20 to 22 g) received an intraperitoneal injection of rhIL-10 (0.2 mu g [n = 20], 2 mu g [n 20], 5 mu g [n = 25], or 20 mu g [n = 15]), and 16 mice received murine anti-IL-10 IgM 200 mu g. T wenty-five additional mice underwent visceral ischemia-reperfusion wit hout treatment (controls), and 16 mice underwent laparotomy without ao rtic occlusion (sham). Results: Pretreatment with exogenous rhIL-10 re sulted in significant reductions in lung neutrophil infiltration with 0.2 mu g, 2 mu g, and 5 mu g per mouse of rhIL-10 compared with lung n eutrophil levels in control mice that underwent acute visceral ischemi a-reperfusion alone (p < 0.05). In addition, serum TNF alpha was detec ted in 50% of control mice and in 75% of mice that received murine ant i-IL-10, but in none of the mice that received rhIL-10 (2 mu g per mou se) or the mice that underwent sham operative procedures (p < 0.05 by chi(2) analysis). Conclusion: Exogenous IL-10 limits pulmonary neutrop hil recruitment and the appearance of TNF alpha in this model of visce ral ischemia-reperfusion injury. Thus the use of exogenous IL-10 may o ffer a novel therapeutic approach to decrease the complications that a re associated with TAAA repair.