The Use of Interferon-α in Virus Infections

Finter, N. B.; Chapman, S.; Dowd, P.; Johnston, J. M.; Manna, V.; Sarantis, N.; Sheron, N.; Scott, G.; Phua, S.; Tatum, P. B.

The interferons (IFN) act too slowly to arrest acute viral infections, but interferon-α (IFNα) 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 IFNα have been identified. There are also 3 slightly different verrions of the same single subtype, IFNα-2, made by recombinant DNA procedures in bacteria. IFNα 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 IFNα-2 than after IFN derived from human cells. Given intranasally, IFTα 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. IFNα 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. IFNα 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 IFNα 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 IFNα 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 IFNα. In patients with chronic hepatitis C, the biochemical markers usually improve rapidly during IFNα 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.