Unsinger Jacqueline, Burnham Carey-Ann D, McDonough Jacquelyn, Morre Michel, Prakash Priya S, Caldwell Charles C, Dunne W Michael, Hotchkiss Richard S
Department of Anesthesiology, Washington University School of Medicine, St Louis, MO 63110, USA.
J Infect Dis. 2012 Aug 15;206(4):606-16. doi: 10.1093/infdis/jis383. Epub 2012 Jun 12.
Secondary hospital-acquired fungal infections are common in critically-ill patients and mortality remains high despite antimicrobial therapy. Interleukin-7 (IL-7) is a potent immunotherapeutic agent that improves host immunity and has shown efficacy in bacterial and viral models of infection. This study examined the ability of IL-7, which is currently in multiple clinical trials (including hepatitis and human immunodeficiency virus), to improve survival in a clinically relevant 2-hit model of fungal sepsis.
Mice underwent cecal ligation and puncture to induce peritonitis. Four days later, surviving mice had intravenous injection with Candida albicans. Following Candida infection, mice were treated with IL-7 or saline control. The effect of IL-7 on host immunity and survival was recorded.
IL-7 ameliorated the loss of immune effector cells and increased lymphocyte functions, including activation, proliferation, expression of adhesion molecules, and interferon-γ production. These beneficial effects of IL-7 were associated with an increase in global immunity as reflected by an enhanced delayed type hypersensitivity response and a 1.7-fold improvement in survival.
The present findings showing that IL-7 improves survival in fungal sepsis, together with its previously reported efficacy in bacterial and viral infectious models, further supports its use as a novel immunotherapeutic in sepsis.
医院获得性继发性真菌感染在重症患者中很常见，尽管进行了抗菌治疗，但死亡率仍然很高。白细胞介素-7（IL-7）是一种有效的免疫治疗药物，可提高宿主免疫力，并已在细菌和病毒感染模型中显示出疗效。本研究考察了目前正在进行多项临床试验（包括肝炎和人类免疫缺陷病毒）的IL-7在临床上相关的真菌性脓毒症二次打击模型中提高生存率的能力。
对小鼠进行盲肠结扎和穿刺以诱导腹膜炎。四天后，存活的小鼠静脉注射白色念珠菌。念珠菌感染后，用IL-7或生理盐水对照治疗小鼠。记录IL-7对宿主免疫力和生存的影响。
IL-7改善了免疫效应细胞的损失，并增强了淋巴细胞功能，包括激活、增殖、黏附分子表达和干扰素-γ产生。IL-7的这些有益作用与整体免疫力的增加相关，这表现为迟发型超敏反应增强和生存率提高1.7倍。
目前的研究结果表明IL-7可提高真菌性脓毒症的生存率，连同其先前在细菌和病毒感染模型中报道的疗效，进一步支持其作为脓毒症新型免疫治疗药物的应用。
