Interleukin 1 receptor antagonist reduces lethality and intestinal toxicity of 5-fluorouracil in a mouse mucositis model.
Chemotherapy-induced intestinal mucositis is still an unmet medical problem. 5-Fluorouracil (5-Fu), a chemotherapy drug, was used to create the animal model of mucositis. Global gene expression array was applied to identify genetic signals involved in the pathogenesis of mucositis. Interleukin 1 receptor antagonist (IL-1Ra) was one of the candidates with the characteristic gene expression profile. Its temporal expression pattern correlated to the damage and regeneration phase of the small intestine after a single injection of 5-Fu to mice. Administration of recombinant IL-1Ra to the mouse model of intestinal mucositis induced by 5-Fu demonstrated its therapeutic effects to the symptoms and pathology of the disease. The IL-1Ra treatment reduced the acute lethality, accelerated their body weight recovery, and eliminated severe diarrhea. The symptomatic benefits were supported by the pathological benefits, in which the mice treated with IL-1Ra had less damage and faster recovery of the structure integrity of their small intestine than that of the mice treated with vehicle control. To deliver the therapeutics to the unmet medical condition, further mechanism and translational studies of IL-1Ra in the settings of chemotherapy-induced intestinal mucositis are warranted.
Wu
Zhenqian
Z
Department of Surgery, The Sixth People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai 200233, PR China.
Han
Xiaodong
X
Qin
Shenyin
S
Zheng
Qi
Q
Wang
Zhigang
Z
Xiang
Di
D
Zhang
Jing
J
Lu
Huili
H
Wu
Mingyuan
M
Zhu
Shunying
S
Yu
Yan
Y
Wang
Yu
Y
Han
Wei
W
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000097:blood / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects; D001835:Body Weight / Q000187:drug effects; D003967:Diarrhea / Q000188:drug therapy; D004195:Disease Models, Animal; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000037:antagonists & inhibitors*; D020869:Gene Expression Profiling / Q000379:methods; D053590:Interleukin 1 Receptor Antagonist Protein / Q000097:blood / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D007421:Intestine, Small / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D052016:Mucositis / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000401:mortality*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D015996:Survival Rate
D000893:Anti-Inflammatory Agents; D000964:Antimetabolites, Antineoplastic; C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D011994:Recombinant Proteins; D005472:Fluorouracil