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Comparison of interleukin-11 and epidermal growth factor on residual small intestine after massive small bowel
N F Fiore1, G Ledniczky, Q Liu
1Department of Surgery, Herman B. Wells Center for Pediatric Research and the Howard Hughes Medical Institute, Indiana University School of Medicine, Indianapolis, USA.
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.
Methods:
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.
Results:
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.
Conclusions:
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.