Effects of interleukin-11 and epidermal growth factor on residual small intestine after experimental massive small bowel resection.

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 (90-100g) 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 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. Body weight was similar at day 4 and 8. Mucosal thickness in groups 11 (IL-11) and IV (IL-11 and EGF) was significantly increased at day 4 and 8 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% in group III and IV. 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 causing proliferation of both enterocytes and myocytes. IL-11, with or without EGF may be a useful adjunct in treatment of short bowel syndrome.