Exogenously administered interleukin-10 decreases pulmonary neutrophil infiltration in a tumor necrosis factor–dependent murine model of acute visceral ischemia

AbstractIntroduction: Visceral ischemia and reperfusion associated with thoracoabdominal aortic aneurysm (TAAA) repair results in lung injury, which appears to be mediated in part by proinflammatory cytokines. The purpose of this study was to determine the effect of exogenous administration of the antiinflammatory cytokine, recombinant human IL-10 (rhIL-10), on proinflammatory cytokine production (IL-6 and TNFα) and pulmonary neutrophil infiltration after acute visceral ischemia-reperfusion.Methods: Two hours before 25 minutes of supraceliac aortic occlusion, 80 C57BL/6 mice (20 to 22 g) received an intraperitoneal injection of rhIL-10 (0.2 μg [n = 20], 2 μg [n = 20], 5 μg [n = 25], or 20 μg [n = 15]), and 16 mice received murine anti-IL-10 IgM 200 μg. Twenty-five additional mice underwent visceral ischemia-reperfusion without treatment (controls), and 16 mice underwent laparotomy without aortic occlusion (sham).Results: Pretreatment with exogenous rhIL-10 resulted in significant reductions in lung neutrophil infiltration with 0.2 μg, 2 μg, and 5 μg per mouse of rhIL-10 compared with lung neutrophil levels in control mice that underwent acute visceral ischemia-reperfusion alone (p < 0.05). In addition, serum TNFα was detected in 50% of control mice and in 75% of mice that received murine anti-IL-10, but in none of the mice that received rhIL-10 (2 μg per mouse) or the mice that underwent sham operative procedures (p < 0.05 by χ 2 analysis).Conclusion: Exogenous IL-10 limits pulmonary neutrophil recruitment and the appearance of TNFα in this model of visceral ischemia-reperfusion injury. Thus the use of exogenous IL-10 may offer a novel therapeutic approach to decrease the complications that are associated with TAAA repair. (J Vasc Surg 1997;26:113-8.