Alteration in the frequency, severity and duration of chemotherapy-induced mucositis in hamsters by interleukin-11

Eur J Cancer B Oral Oncol. 1995 Jul;31B(4):261-6. doi: 10.1016/0964-1955(95)00015-a.

Abstract

Ninety-five young, male Golden Syrian hamsters were randomly divided into five equally sized groups. One group served as a placebo control while the animals in the others received one of four doses of interleukin-eleven (IL-11) twice daily given by subcutaneous injection beginning on the first day of chemotherapy (day 0) and continuing to day 14. Mucositis was induced with 5-fluorouracil using a standard regimen of 60 mg/kg, intraperitoneally on days 0 and 2 followed by superficial mucosal irritation on day 4. Animals were evaluated daily beginning on day 6. Mucositis was assessed using a standardised technique in which randomly numbered daily mucosal photographs were scored by three blinded independent observers at the conclusion of the experiment. IL-11 favourably affected the frequency, severity and duration of mucositis. This phenomenon appeared to be dose dependent. Hamsters receiving 30 and 100 micrograms per day of IL-11 demonstrated significantly (P < 0.05) lower mucositis scores than did either the control or animals receiving 3 or 10 micrograms per day, although the latter had marginal beneficial effects. Additionally, survival was significantly better for hamsters receiving higher doses of IL-11 (85%) compared to the placebo control (46%). IL-11 administration also favourably affected weight loss. While stimulation of platelet production was noted in animals receiving IL-11, a lack of difference in bone marrow cellularity between test and control animals suggests that the mechanism by which IL-11 modifies mucositis is mediated at the epithelial or connective tissue level rather than through the marrow. The kinetics of IL-11 alteration of mucositis induction supports such a hypothesis. Further investigation is currently underway to establish a definitive mechanism by which IL-11 protects the oral mucosa.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimetabolites, Antineoplastic / adverse effects*
  • Bone Marrow / pathology
  • Cricetinae
  • Dose-Response Relationship, Drug
  • Fluorouracil / adverse effects*
  • Interleukin-11 / therapeutic use*
  • Male
  • Mesocricetus
  • Mouth Mucosa
  • Platelet Count
  • Recombinant Proteins / therapeutic use
  • Stomatitis / chemically induced
  • Stomatitis / pathology
  • Stomatitis / prevention & control*
  • Survival Rate
  • Weight Loss

Substances

  • Antimetabolites, Antineoplastic
  • Interleukin-11
  • Recombinant Proteins
  • Fluorouracil