Mitigating effects of interleukin 11 on consecutive courses of 5-fluorouracil-induced ulcerative mucositis in hamsters.
Ulcerative mucositis is a painful, debilitating and dose-limiting toxicity of cancer chemotherapy. Current treatment is largely palliative and no adequate preventive treatment exists. Recently, we reported that recombinant human(rh) interleukin 11 (IL-11) favourably modified the course of mucositis following a single stomatotoxic regimen of 5-fluorouracil in hamsters. Although potentially beneficial, the clinically relevant issue of mucositis and myelosuppression during multicourse chemotherapy treatment was not addressed. The present study was undertaken to evaluate the effect of rhIL-11 on two consecutive courses of mucositis and myelosuppression in hamsters. Ulcerative mucositis was induced using a standardized protocol consisting of 5-fluorouracil (60 mg/kg) on days 1 and 2 followed by superficial irritation of the buccal mucosa on day 4. Animals treated with 100 microg of rhIL-11 for 12 consecutive days following each regimen of chemotherapy experienced a reduction in the incidence, severity, and duration of mucositis, a reduction in weight loss, and less morbidity and mortality relative to control animals. Bone marrow cellularity and function was not adversely affected by rhIL-11 treatment. The present study is consistent with the potential use of rhIL-11 treating patients at risk of developing ulcerative mucositis while undergoing intensive multicourse chemotherapy treatment.
Sonis
S T
ST
Division of Oral Medicine Oral and Maxillofacial Surgery, and Dentistry, Brigham & Women's Hospital, Boston, MA 02115, USA.
Van Vugt
A G
AG
McDonald
J
J
Dotoli
E
E
Schwertschlag
U
U
Szklut
P
P
Keith
J
J
D000818:Animals; D001772:Blood Cell Count; D001854:Bone Marrow Cells; D006224:Cricetinae; D005472:Fluorouracil; D017370:Interleukin-11 / Q000627:therapeutic use*; D008297:Male; D008647:Mesocricetus; D009061:Mouth Mucosa / Q000187:drug effects; D019226:Oral Ulcer / Q000139:chemically induced / Q000188:drug therapy*; D013280:Stomatitis / Q000139:chemically induced / Q000188:drug therapy*; D015431:Weight Loss
D017370:Interleukin-11; D005472:Fluorouracil