Alteration in the frequency, severity and duration of chemotherapy-induced mucositis in hamsters by interleukin-11.
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.
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects*; D001853:Bone Marrow / Q000473:pathology; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D005472:Fluorouracil / Q000009:adverse effects*; D017370:Interleukin-11 / Q000627:therapeutic use*; D008297:Male; D008647:Mesocricetus; D009061:Mouth Mucosa; D010976:Platelet Count; D011994:Recombinant Proteins / Q000627:therapeutic use; D013280:Stomatitis / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D015996:Survival Rate; D015431:Weight Loss
D000964:Antimetabolites, Antineoplastic; D017370:Interleukin-11; D011994:Recombinant Proteins; D005472:Fluorouracil