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Abstract

Gastrointestinal mucositis after cancer chemotherapy is an increasing problem that is essentially untreatable once established, although it gradually remits. The aim of this study was to investigate the time-course and effect of interleukin-11 (IL-11) on apoptosis and intestinal morphometry as measures of mucositis. Female DA rats were implanted subcutaneously with syngeneic breast cancer and treated with methotrexate (MTX). Intestinal morphometry was used to assess villus area, crypt length, and mitotic count per crypt. Apoptosis was assessed by TUNEL assay in the tumor and jejunum. Tumor proliferation was assessed by mitotic count. The time-course study showed that MTX increased apoptosis by 28-fold in the crypts of the small intestine and by 3-fold in the tumor, and peaked at 6 hr after chemotherapy. IL-11 (100 microg/kg/twice daily subcutaneously) maintained intestinal weight, and reduced the severity of mucositis, as measured by villus area, crypt length, and mitotic count per crypt. IL-11 at higher doses (200 microg and 400 microg/kg/twice daily subcutaneously), did not further improve villus area, crypt length, and mitotic count per crypt. IL-11 did not affect tumor apoptosis or proliferation. We conclude that IL-11 attenuated mucositis by maintaining intestinal weight and morphometry. IL-11 did not prevent apoptosis, but rather induced compensatory crypt cell proliferation.

Interaction between Host Cells and Microbes in Chemotherapy-Induced Mucositis

“…Diarrhoea and constipation are thought to be caused by the alteration in absorptive functions of cells, goblet cell and mucin distribution and composition, and bacterial interactions with these cells and metabolites of the drugs themselves [6,7]. Cytotoxic drugs are known to act by inducing apoptosis in cancer; apoptosis is also induced in the GIT [8,9,10]. There are limited ways the mucosa and underlying layers of the GIT can respond to damage.…”

Irinotecan disrupts tight junction proteins within the gut

“…All rats received breast cancer inoculum as described previously. 49,50 Briefly, mammary adenocarcinoma tumors syngeneic with the DA rat were diced, homogenized and filtered through sterile gauze. A viable cell count was conducted using 0.4% w/v trypan blue before 150 μl of cells were implanted subcutaneously into both right and left flanks of the rat at a concentration of 2.0 × 10 7 cells/mL.…”

Correlation between Plasma Glucagon-Like Peptide 2 Levels and Proliferative Makers in Small Intestinal Injury in Rats Induced by Methotrexate Administration

“…[8][9][10][11] Glucagon-like peptide 2 (GLP-2) has been demonstrated to have intestinotrophic effects. 12) GLP-2, a 33-amino acid peptide member of a family of proglucagon-derived peptides (PGDP) that also includes enteroglucagon, is secreted from L-type entero-endocrine cells of the distal small intestine and colon.…”