[Interferons: physiology, pharmacology and pharmacotherapeutic perspectives]

The interferon system was discovered as an antiviral defense mechanism of all higher animals. It is in many aspects complementary to the immune system in that it operates as a first line defense against virus infections by limiting viral replication wherever it occurs in the organism, hereby delaying spread of virus through the body and allowing time for the immune response to develop and become operative in due course. Studies in experimental animals and in man have indicated that administration of exogenous interferon can prevent viral disease if the interferon reaches the crucial sites of viral replication in sufficient concentration and before the virus replication starts. This fact constitutes the main impediment for interferon to become an important antiviral drug. In all animal species that have been examined, there exist multiple genes for interferon. Currently, three types (alpha, beta and gamma) of interferon are distinguished, the genes of which share minor part of their sequences. Each type can in principle comprise several subtypes which share major parts of their sequences. Interferons act on cells by altering their biochemical programming. Thereby they exert multiple cellular effects other than inhibiting virus replication. Cell growth and regeneration of organs is retarded; cells of the immune system are affected in various ways and, as a result of this, the immune system can be stimulated or suppressed depending on the experimental or clinical conditions. Some aspects of this immunoregulatory effect have led to the belief that interferon therapy might be beneficial for tumor patients. In animal systems the antitumor effect of interferon is real but limited in scope : tumors can be delayed in outgrowth but cannot be caused to regress. In clinical trials, mostly involving terminal or preterminal cancer patients, encouraging but unconvincing results have been obtained. This type of investigation is now entering into a stage where amounts of interferon can be given, comparable to those used for animal studies. Moreover, the various types and subtypes of interferon can now be produced in pure form, allowing to test them separately. It is not excluded that from these investigations, new approaches for antitumor therapy will emerge. As regulators of the immune response, interferons may play an important role in auto-immune diseases.(ABSTRACT TRUNCATED AT 400 WORDS)