Finter N B, Chapman S, Dowd P, Johnston J M, Manna V, Sarantis N, Sheron N, Scott G, Phua S, Tatum P B
Wellcome Research Laboratories, Beckenham, Kent, England.
Drugs. 1991 Nov;42(5):749-65. doi: 10.2165/00003495-199142050-00003.
The interferons (IFN) act too slowly to arrest acute viral infections, but interferon-alpha (IFN alpha) preparations have proved useful in some chronic infections and will clearly be used increasingly in these in the future. In the preparations derived from human leucocytes or cultured B lymphoblastoid cells, which are in routine clinical use, mixtures of a number of distinct subtypes of human IFN alpha have been identified. There are also 3 slightly different versions of the same single subtype, IFN alpha-2, made by recombinant DNA procedures in bacteria. IFN alpha preparations are injected intramuscularly or subcutaneously. Dose-related side effects are common but usually tolerable, but prolonged treatment may cause increasing fatigue and depression. Some patients form neutralising antibodies which block the effects of the IFN; these appear to be relatively more common after recombinant IFN alpha-2 than after IFN derived from human cells. Given intranasally, IFN alpha can prevent a subsequent experimental rhinovirus infection, or the spread of natural colds within a family. Repeated administration progressively damages the nasal mucosa, so that long term prophylaxis is not possible. IFN alpha has proved useful in patients with papillomavirus warts of the larynx, ano-genital region (condyloma acuminata) and skin (common warts). Treatment regimens remain to be optimised and are likely to include surgery or other treatments. IFN alpha and zidovudine (azidothymidine) synergistically inhibit the growth of HIV in vitro, and combination are on trial in patients with early AIDS. Very large doses of IFN alpha are effective against Kaposi's sarcoma in some AIDS patients. In chronic hepatitis B, continuing virus replication may lead to cirrhosis or primary liver cancer. Earlier clinical trials with IFN alpha gave inconclusive results, but recent large studies have confirmed that 25 to 40% of patients obtain benefit; this probably results from both the antiviral and the immunomodulatory effects of IFN alpha. In patients with chronic hepatitis C, the biochemical markers usually improve rapidly during IFN alpha administration, but relapse if treatment is stopped after only a few months; to increase the chances of sustained cure, the treatment period is now being prolonged.
干扰素（IFN）发挥作用的速度过慢，无法阻止急性病毒感染，但α干扰素（IFNα）制剂已被证明在某些慢性感染中有用，且未来显然会在这些疾病中得到越来越多的应用。在常规临床使用的源自人白细胞或培养的B淋巴母细胞的制剂中，已鉴定出多种不同亚型的人IFNα的混合物。通过细菌中的重组DNA程序，还制备出了同一单一亚型IFNα-2的3种略有不同的版本。IFNα制剂通过肌肉注射或皮下注射给药。剂量相关的副作用很常见，但通常可以耐受，不过长期治疗可能会导致疲劳和抑郁加剧。一些患者会形成中和抗体，从而阻断IFN的作用；这些抗体在重组IFNα-2之后似乎比源自人细胞的IFN更为常见。经鼻内给药，IFNα可以预防随后的实验性鼻病毒感染，或预防家庭内自然感冒的传播。反复给药会逐渐损害鼻黏膜，因此无法进行长期预防。IFNα已被证明对患有喉、肛门生殖器区域（尖锐湿疣）和皮肤（寻常疣）乳头瘤病毒疣的患者有用。治疗方案仍有待优化，可能会包括手术或其他治疗方法。IFNα和齐多夫定（叠氮胸苷）在体外协同抑制HIV的生长，目前正在对早期艾滋病患者进行联合试验。非常大剂量的IFNα对一些艾滋病患者的卡波西肉瘤有效。在慢性乙型肝炎中，持续的病毒复制可能会导致肝硬化或原发性肝癌。早期使用IFNα的临床试验结果尚无定论，但最近的大型研究证实，25%至40%的患者会从中受益；这可能是IFNα的抗病毒和免疫调节作用共同导致的。在慢性丙型肝炎患者中，在给予IFNα期间，生化指标通常会迅速改善，但如果仅治疗几个月后就停药则会复发；为了增加持续治愈的机会，目前正在延长治疗期。
