Department of Surgery, Section of Pediatric Surgery, Indianapolis, Indiana; The Indiana University School of Medicine, Indianapolis, Indiana.
Department of Surgery, Section of Pediatric Surgery, Indianapolis, Indiana; The Indiana University School of Medicine, Indianapolis, Indiana; Riley Hospital for Children at Indiana University Health, Indianapolis, Indiana.
J Surg Res. 2019 Jul;239:142-148. doi: 10.1016/j.jss.2019.02.001. Epub 2019 Mar 1.
Interleukin-6 (IL6) has both proinflammatory and anti-inflammatory pathways, but its effects on intestinal recovery following ischemia are unknown. We hypothesized that administration of IL6 following intestinal ischemia would improve mesenteric perfusion and mucosal injury.
Adult male C57Bl6J mice were anesthetized, and a laparotomy was performed. Baseline intestinal perfusion was assessed by laser Doppler imaging. Intestinal ischemia was induced for 60 min by temporarily occluding the superior mesenteric artery. After ischemia, treatments were administered intraperitoneally before closure (Vehicle: 250 μL phosphate-buffered-saline, IL6 low dose (20 ng), IL6 medium dose (200 ng), or IL6 high dose (2 μg)). Animals were allowed to recover for 24 h, were reanesthetized, and their mesenteric perfusion was reassessed. Perfusion was expressed as percentage of baseline. Animals were then sacrificed, and the intestines were explanted for histological analysis. Separate frozen samples were homogenized and analyzed by ELISA for vascular endothelial growth factor (VEGF) and interferon gamma-induced protein 10.
IL6 increased mesenteric perfusion in low dose groups only, whereas it improved postischemic mucosal injury scores in both low and medium dose groups. No differences in perfusion or histology were seen when high dose IL6 was utilized. Intestinal VEGF was higher in the low dose IL6 group compared to vehicle, whereas IP-10 levels were lower in low and medium dose groups compared to vehicle. No differences were noted compared to vehicle in intestinal VEGF and IP-10 with high dose IL6 therapy.
Lower doses of IL6 may serve as effective therapy to decrease intestinal injury after ischemia. Further studies are needed to elucidate the downstream mechanisms before widespread clinical use.
白细胞介素 6（IL6）具有促炎和抗炎途径，但它对缺血后肠道恢复的影响尚不清楚。我们假设在肠缺血后给予 IL6 会改善肠系膜灌注和黏膜损伤。
成年雄性 C57Bl6J 小鼠麻醉后行剖腹术。通过激光多普勒成像评估基础肠道灌注。通过暂时阻断肠系膜上动脉缺血 60 分钟来诱导肠缺血。缺血后，在关闭前经腹腔内给药（载体：250μL 磷酸盐缓冲盐水、IL6 低剂量（20ng）、IL6 中剂量（200ng）或 IL6 高剂量（2μg））。动物恢复 24 小时后，重新麻醉，再次评估肠系膜灌注。灌注以基础值的百分比表示。然后处死动物，取出肠道进行组织学分析。分离的冷冻样本匀浆后通过 ELISA 分析血管内皮生长因子（VEGF）和干扰素γ诱导蛋白 10。
IL6 仅在低剂量组中增加肠系膜灌注，而在低剂量和中剂量组中均改善了缺血后黏膜损伤评分。高剂量 IL6 组未观察到灌注或组织学差异。与载体相比，低剂量 IL6 组的肠道 VEGF 更高，而低剂量和中剂量组的 IP-10 水平均低于载体。与载体相比，高剂量 IL6 治疗组的肠道 VEGF 和 IP-10 无差异。
较低剂量的 IL6 可能是治疗缺血后肠道损伤的有效方法。需要进一步的研究来阐明广泛临床应用之前的下游机制。
