Holland S M
Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Adv Intern Med. 2000;45:431-52.
More than a century after the discovery of tuberculosis, mycobacterial infections are resurgent. The recent identification of mutations affecting the control of mycobacteria offer critical insights into the pathways necessary for the control of intracellular pathogens and bring us several steps closer to understanding the basic mechanisms involved. Therapy, which until recently seemed simple and straightforward, is now complicated by the emergence of drug-resistant organisms and immunocompromised hosts. Despite these problems, multidrug therapy remains the mainstay of successful treatment. Adjuvant cytokines such as IL-2, IFN-gamma, IL-12, and GM-CSF hold great promise for shortening the duration of treatment and overcoming drug resistance. Control of cytokine production by agents such as thalidomide opens the door to selective control of deleterious parts of the inflammatory response while effective drug treatment is instituted. Modulation of the host response in the fight against mycobacteria will be the focus of the next decades, and it promises to be at the forefront of immunotherapeutics.
在结核病被发现一个多世纪后，分枝杆菌感染再度抬头。最近对影响分枝杆菌控制的突变的鉴定，为了解控制细胞内病原体所需的途径提供了关键见解，并使我们在理解相关基本机制方面又迈进了几步。直到最近看起来简单直接的治疗方法，如今因耐药菌和免疫功能低下宿主的出现而变得复杂。尽管存在这些问题，多药疗法仍然是成功治疗的主要手段。诸如白细胞介素-2、干扰素-γ、白细胞介素-12和粒细胞巨噬细胞集落刺激因子等辅助性细胞因子，在缩短治疗时间和克服耐药性方面有着巨大潜力。沙利度胺等药物对细胞因子产生的控制，为在进行有效药物治疗时选择性控制炎症反应的有害部分打开了大门。在对抗分枝杆菌的过程中调节宿主反应将是未来几十年的重点，并且有望处于免疫治疗的前沿。
