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 i nto five equally sized groups, One group served as a placebo control w hile the animals in the others received one of four doses of interleuk in-eleven (IL-11) twice daily given by subcutaneous injection beginnin g on the first day of chemotherapy (day 0) and continuing to day 14. M ucositis was induced with 5-fluorouracil using a standard regimen of 6 0 mg/kg, intraperitoneally on days 0 and 2 followed by superficial muc osal irritation on day 4, Animals were evaluated daily beginning on da y 6, Mucositis was assessed using a standardised technique in which ra ndomly numbered daily mucosal photographs were scored by three blinded independent observers at the conclusion of the experiment, IL-11 favo urably affected the frequency, severity and duration of mucositis. Thi s phenomenon appeared to be dose dependent, Hamsters receiving 30 and 100 mu g per day of IL-ll demonstrated significantly (P<0.05) lower mu cositis scores than did either the control or animals receiving 3 or 1 0 mu g per day, although the latter had marginal beneficial effects, A dditionally, 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 stimulat ion of platelet production was noted in animals receiving IL-11, a lac k of difference in bone marrow cellularity between test and control an imals suggests that the mechanism by which][L-ll modifies mucositis is mediated at the epithelial or connective tissue level rather than thr ough the marrow. The kinetics of IL-11 alteration of mucositis inducti on supports such a hypothesis, Further investigation is currently unde rway to establish a definitive mechanism by which IL-11 protects the o ral mucosa.