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白细胞介素11对仓鼠连续疗程5-氟尿嘧啶诱导的溃疡性粘膜炎的缓解作用。

Mitigating effects of interleukin 11 on consecutive courses of 5-fluorouracil-induced ulcerative mucositis in hamsters.

作者信息

Sonis S T, Van Vugt A G, McDonald J, Dotoli E, Schwertschlag U, Szklut P, Keith J

机构信息

Division of Oral Medicine Oral and Maxillofacial Surgery, and Dentistry, Brigham & Women's Hospital, Boston, MA 02115, USA.

出版信息

Cytokine. 1997 Aug;9(8):605-12. doi: 10.1006/cyto.1997.0208.

Abstract

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.

摘要

溃疡性粘膜炎是癌症化疗中一种疼痛、使人虚弱且限制剂量的毒性反应。目前的治疗主要是姑息性的,且尚无充分的预防性治疗方法。最近,我们报道了重组人(rh)白细胞介素11(IL-11)可使仓鼠在接受单次5-氟尿嘧啶口腔毒性治疗方案后粘膜炎的病程得到有利改善。尽管可能有益,但多疗程化疗治疗期间粘膜炎和骨髓抑制这一临床相关问题尚未得到解决。本研究旨在评估rhIL-11对仓鼠连续两个疗程的粘膜炎和骨髓抑制的影响。使用标准化方案诱导溃疡性粘膜炎,即在第1天和第2天给予5-氟尿嘧啶(60mg/kg),随后在第4天对颊粘膜进行轻度刺激。在每次化疗方案后连续12天用100μg rhIL-11治疗的动物,与对照动物相比,粘膜炎的发生率、严重程度和持续时间均有所降低,体重减轻减少,发病率和死亡率也更低。rhIL-11治疗对骨髓细胞数量和功能没有不利影响。本研究结果表明,rhIL-11有可能用于治疗在接受强化多疗程化疗治疗时发生溃疡性粘膜炎风险的患者。

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