Fiore N F, Ledniczky G, Liu Q, Orazi A, Du X, Williams D A, Grosfeld J L
Department of Surgery, Herman B. Wells Center for Pediatric Research and the Howard Hughes Medical Institute, Indiana University School of Medicine, Indianapolis, USA.
J Pediatr Surg. 1998 Jan;33(1):24-9. doi: 10.1016/s0022-3468(98)90354-2.
BACKGROUND/PURPOSE: Interleukin-11 (IL-11) is a multifunctional cytokine derived from bone marrow, which has a trophic effect on small bowel epithelium. This study compares the effects of IL-11 with epidermal growth factor (EGF), a growth factor known to enhance small bowel adaptation.
Forty Sprague-Dawley rats (90 to 100 g) underwent an 85% mid-small bowel resection with primary anastomosis on day 0. Rats were divided into four treatment groups: controls (group I) received bovine serum albumin (BSA), group II received IL-11, 125 microg/kg subcutaneously (SC) twice daily, group III received EGF, 0.10 microg/g SC bid, and group IV received EGF and IL-11 in the above doses. Half of the animals (five per group) were killed on day 4 of therapy, and the rest were killed on day 8. Animals were evaluated for weight, mucosal length, and bowel wall muscle thickness on days 4 and 8, and expression of proliferating cell nuclear antigen (PCNA) in intestinal crypt and smooth muscle cells on day 8.
There were two deaths; both were 8-day controls. Body weight was similar at day 4 and day 8. Mucosal thickness in groups II (IL-11) and group IV (IL-11 and EGF) was significantly increased at day 4 and 8 when compared with controls (group I) and EGF (group III, P < .001). Muscle thickness was significantly increased in the EGF and combined group IV compared with the BSA controls and IL-11 groups (P < .001). Thirty-two percent of the mucosal crypt cells in Group I stained positive for PCNA, whereas 51%, 53%, and 60% stained positive in groups II (IL-11), III (EGF), and IV (IL-11 and EGF), respectively. In groups I and II, 2% and 1.7% of the myocytes stained positive for PCNA, whereas 11.2% and 5.2% of the myocytes in group III and IV stained positive.
These data suggest that IL-11 has a trophic effect on small intestinal enterocytes, causing cell proliferation and increased mucosal thickness. EGF has a more generalized effect on intestine causing proliferation of both enterocytes and myocytes. IL-11, with or without EGF, may be a useful adjunct in instances of short bowel syndrome.
背景/目的:白细胞介素-11(IL-11)是一种源自骨髓的多功能细胞因子,对小肠上皮具有营养作用。本研究比较了IL-11与表皮生长因子(EGF)的作用,EGF是一种已知可增强小肠适应性的生长因子。
40只Sprague-Dawley大鼠(90至100克)于第0天接受85%的小肠中段切除并一期吻合。大鼠被分为四个治疗组:对照组(I组)接受牛血清白蛋白(BSA);II组接受IL-11,125微克/千克皮下注射(SC),每日两次;III组接受EGF,0.10微克/克皮下注射,每日两次;IV组接受上述剂量的EGF和IL-11。治疗第4天处死一半动物(每组5只),其余在第8天处死。在第4天和第8天评估动物的体重、黏膜长度和肠壁肌肉厚度,并在第8天评估肠隐窝和平滑肌细胞中增殖细胞核抗原(PCNA)的表达。
有2只死亡;均为第8天的对照组动物。第4天和第8天体重相似。与对照组(I组)和EGF组(III组)相比,II组(IL-11)和IV组(IL-11和EGF)在第4天和第8天的黏膜厚度显著增加(P <.001)。与BSA对照组和IL-11组相比,EGF组和IV联合组的肌肉厚度显著增加(P <.001)。I组32%的黏膜隐窝细胞PCNA染色呈阳性,而II组(IL-11)、III组(EGF)和IV组(IL-11和EGF)分别为51%、53%和60%。在I组和II组中,2%和1.7%的肌细胞PCNA染色呈阳性,而III组和IV组分别为11.2%和5.2%。
这些数据表明,IL-11对小肠肠上皮细胞具有营养作用,可导致细胞增殖并增加黏膜厚度。EGF对肠道具有更广泛的作用,可导致肠上皮细胞和平滑肌细胞均增殖。无论有无EGF,IL-11在短肠综合征病例中可能是一种有用的辅助治疗手段。