RÉSUMÉ
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 has 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.
Sujet(s)
Fluorouracil/toxicité , Antagoniste du récepteur à l'interleukine-1/pharmacologie , Muqueuse intestinale/effets des médicaments et des substances chimiques , Inflammation muqueuse/induit chimiquement , Inflammation muqueuse/traitement médicamenteux , Animaux , Poids/effets des médicaments et des substances chimiques , Diarrhée/prévention et contrôle , Modèles animaux de maladie humaine , Interactions médicamenteuses , Femelle , Analyse de profil d'expression de gènes/méthodes , Antagoniste du récepteur à l'interleukine-1/biosynthèse , Antagoniste du récepteur à l'interleukine-1/génétique , Muqueuse intestinale/métabolisme , Muqueuse intestinale/anatomopathologie , Intestin grêle/effets des médicaments et des substances chimiques , Intestin grêle/métabolisme , Intestin grêle/anatomopathologie , Mâle , Souris , Souris de lignée BALB C , Inflammation muqueuse/génétique , Inflammation muqueuse/anatomopathologie , Protéines recombinantes/génétique , Protéines recombinantes/métabolisme , Protéines recombinantes/pharmacologieRÉSUMÉ
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.