Kullberg B J, van 't Wout J W
Department of Medicine, University Hospital Nijmegen, The Netherlands.
Biotherapy. 1994;7(3-4):195-210. doi: 10.1007/BF01878486.
The incidence of invasive fungal infections in the immunocompromized host has increased during the past decade. Even the recently developed antifungal drugs are unable to cure these infections in patients with severely impaired host defense mechanisms. Cytokines have great potential to augment host resistance and as adjunctive therapy of invasive mycoses. We discuss the mechanisms of host defense against invasive candidiasis, aspergillosis, and cryptococcosis, and review the use of cytokines and growth factors in this setting. Interleukin-1 has been shown effective in an animal model of disseminated candidiasis, even during severe granulocytopenia. Interferon-gamma has been very effective as a modulator of resistance against a variety of fungal infections in vitro. The effect of interferon-gamma against disseminated candidiasis has been demonstrated in a mouse model. Activation of neutrophils is the main mechanism by which interferon-gamma enhances the elimination of Candida, and consequently the agent is not effective in severely granulocytopenic animals. Data on the role of colony-stimulating factors against fungal pathogens are accumulating, and trials with these agents for hematologic patients with invasive fungal infections are now being performed.
在过去十年中，免疫功能低下宿主侵袭性真菌感染的发生率有所上升。即便最近研发的抗真菌药物也无法治愈宿主防御机制严重受损患者的这些感染。细胞因子在增强宿主抵抗力以及作为侵袭性真菌病辅助治疗方面具有巨大潜力。我们讨论宿主抵御侵袭性念珠菌病、曲霉病和隐球菌病的机制，并综述细胞因子和生长因子在此情况下的应用。白细胞介素-1已在播散性念珠菌病动物模型中显示有效，即便在严重粒细胞减少期间。γ干扰素作为体外抗多种真菌感染的抵抗力调节剂非常有效。γ干扰素对播散性念珠菌病的作用已在小鼠模型中得到证实。中性粒细胞的激活是γ干扰素增强念珠菌清除的主要机制，因此该药物在严重粒细胞减少的动物中无效。关于集落刺激因子对真菌病原体作用的数据正在积累，目前正在对侵袭性真菌感染的血液病患者进行这些药物的试验。
