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.