Effect of interleukin-11 on ameliorating intestinal damage after methotrexate treatment of breast cancer in rats.
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.
Gibson
Rachel J
RJ
Department of Medical Oncology, The Royal Adelaide Hospital, Adelaide, South Australia, Australia.
Keefe
Dorothy M K
DM
Thompson
Fiona M
FM
Clarke
Julie M
JM
Goland
Gary J
GJ
Cummins
Adrian G
AG
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D005260:Female; D017370:Interleukin-11 / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D008727:Methotrexate / Q000009:adverse effects* / Q000627:therapeutic use; D009929:Organ Size; D051381:Rats; D011919:Rats, Inbred Strains
D000964:Antimetabolites, Antineoplastic; D017370:Interleukin-11; D008727:Methotrexate