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

Hess PJ, Seeger JM, Huber TS, Welborn MB, Martin TD, Harward TR, Duschek S, Edwards PD, Solorzano CC, Copeland EM, Moldawer LL
J Vasc Surg. 1997 26 (1): 113-8

PMID: 9240329 · DOI:10.1016/s0741-5214(97)70154-x

INTRODUCTION - 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 TNF alpha) 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 microgram [n = 20], 2 micrograms [n = 20], 5 micrograms [n = 25], or 20 micrograms [n = 15]), and 16 mice received murine anti-IL-10 IgM 200 micrograms. 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 microgram, 2 micrograms, and 5 micrograms 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 TNF alpha 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 micrograms per mouse) or the mice that underwent sham operative procedures (p < 0.05 by chi 2 analysis).

CONCLUSION - Exogenous IL-10 limits pulmonary neutrophil recruitment and the appearance of TNF alpha 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.

MeSH Terms (18)

Acute Disease Animals Aorta Cell Movement Constriction Female Immunoglobulin M Interleukin-6 Interleukin-10 Lung Mice Mice, Inbred C57BL Neutrophils Peroxidase Recombinant Proteins Reperfusion Injury Tumor Necrosis Factor-alpha Viscera

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