Chadha Kailash C, Ambrus Julian L, Dembinski Wlodzimierz, Ambrus Julian L
Department of Molecular & Cellular Biology, Roswell Park Cancer Institute, State University of New York at Buffalo, Buffalo, New York 14203, USA.
Exp Biol Med (Maywood). 2004 Apr;229(4):285-90. doi: 10.1177/153537020422900402.
Interferon (IFN) resistance is an important factor in the pathophysiology of neoplastic disorders, certain viral infections (e.g., AIDS), and autoimmune diseases (e.g., lupus erythematosus and Wegner's granulomatosis). In addition, in some of these disorders, there is also decreased ability to produce IFNs. The capacity of viruses and neoplastic processes to interfere with the IFN system are thought to represent a "virus-against-host" or "cancer-against-host" defense mechanism. Four resistance factors have been identified: 1) release of free IFN-alpha/beta type 1 receptors into the circulation that, at appropriate concentrations, capture and inactivate IFNs; 2) a new IFN inhibitory protein has been isolated and its chemical structure is under study; 3) prostaglandin E2, which is produced by certain tumor cells, inhibits IFN production; and 4) high levels of cAMP phosphodiesterases present, for example in certain tumor cells, reduces cAMP, an important second messenger in IFN synthesis. Studies are under way to reverse these inhibitory effects and to increase endogenous interferon production.
干扰素（IFN）抵抗是肿瘤性疾病、某些病毒感染（如艾滋病）和自身免疫性疾病（如红斑狼疮和韦格纳肉芽肿病）病理生理学中的一个重要因素。此外，在其中一些疾病中，产生干扰素的能力也会下降。病毒和肿瘤过程干扰干扰素系统的能力被认为代表了一种“病毒对抗宿主”或“癌症对抗宿主”的防御机制。已确定了四个抵抗因素：1）游离的1型干扰素α/β受体释放到循环中，在适当浓度下捕获并使干扰素失活；2）一种新的干扰素抑制蛋白已被分离出来，其化学结构正在研究中；3）某些肿瘤细胞产生的前列腺素E2抑制干扰素的产生；4）例如在某些肿瘤细胞中存在的高水平环磷酸腺苷磷酸二酯酶会降低环磷酸腺苷，而环磷酸腺苷是干扰素合成中的一种重要第二信使。目前正在进行研究以逆转这些抑制作用并增加内源性干扰素的产生。
