Opal Steven M, Keith James C, Jhung Jhung, Palardy John E, Parejo Nicolas, Marchese Erik, Maganti Vasu
Infectious Disease Division and Department of Pathology, Memorial Hospital of Rhode Island and Brown University School of Medicine, Providence 02860, USA.
J Infect Dis. 2003 Jan 1;187(1):70-6. doi: 10.1086/345864. Epub 2002 Dec 13.
Recombinant human interleukin (IL)-11 is a multifunctional cytokine with hematopoietic, immunomodulatory, and epithelial cell protective activities. IL-11alpha receptors are expressed on the luminal surface of intestinal epithelial cells. It was hypothesized that orally administered IL-11 would prevent mucosal damage and protect against microbial invasion in a neutropenic rat model of gram-negative sepsis. IL-11 was administered daily by enteric, coated multiparticle pellets over the course of chemotherapy-induced neutropenia. Compared with the placebo group, IL-11-treated rats retained mucosal mass and had prolonged survival time, reduced pathologic changes, and reduced systemic levels of bacterial endotoxin and concentrations of Pseudomonas aeruginosa in target tissues. Enterocyte messenger RNA levels for tumor necrosis factor-alpha and interferon-gamma revealed that oral IL-11 reduced but did not prevent increased expression of these cytokine genes. These results indicate that orally administered IL-11 may preserve epithelial cell integrity in the presence of cytoreductive chemotherapy. This may represent a new treatment strategy for the prevention of infection in neutropenic hosts.
重组人白细胞介素（IL）-11是一种具有造血、免疫调节和上皮细胞保护活性的多功能细胞因子。IL-11α受体表达于肠道上皮细胞的管腔表面。有研究假设，在革兰氏阴性脓毒症中性粒细胞减少大鼠模型中，口服IL-11可预防黏膜损伤并抵御微生物入侵。在化疗诱导的中性粒细胞减少过程中，通过肠溶包衣多颗粒微丸每日给予IL-11。与安慰剂组相比，接受IL-11治疗的大鼠保留了黏膜质量，延长了生存时间，减少了病理变化，降低了全身细菌内毒素水平以及靶组织中铜绿假单胞菌的浓度。肿瘤坏死因子-α和干扰素-γ的肠上皮细胞信使核糖核酸水平显示，口服IL-11可降低但不能阻止这些细胞因子基因表达的增加。这些结果表明，在进行细胞减灭性化疗时，口服IL-11可能维持上皮细胞的完整性。这可能代表了一种预防中性粒细胞减少宿主感染的新治疗策略。
