The pharmacology and toxicology of the interferons: an overview.

Interferon was discovered three decades ago. The next 20 or more years of research were directed largely toward an understanding of its antiviral activity. The persistent short supply of interferon hampered progress, and the impure preparations available throughout these years clouded interpretation of results. Many of the experiments and clinical studies that interferonologists had dreamed of for 20 or more years became realities when modern technology provided quantities of pure interferon that exceeded expectations. Studies with these pure recombinant interferons removed all doubts that the many pleiotropic effects that had been observed with impure interferon preparations were due to interferon and not to the impurities. The interferons are now acknowledged lymphokines that are involved in many cellular processes. In fact, the antiviral activity of interferon, which led to its discovery, may be an exaggerated adaptive utilization of an interferon-regulated function that plays a more general role in cellular physiology. The ability to isolate, purify, and produce pure interferon has led to the discovery of multiple species of leukocyte interferon. These interferons display different patterns of activity when tested by a variety of systems. This suggests that specific leukocyte interferons may be involved in specific physiological functions. Results of preliminary trials of the interferons as antiviral and antitumor agents have been encouraging and occasionally dramatic. The overall clinical picture is expected to improve when more is learned about the pharmacokinetics of the interferons and which of the interferons are best suited for the treatment of specific tumors and antiviral diseases. There are indications that coadministration of interferons with chemical antineoplastic and antiviral agents may increase the effectiveness of interferon in clinical situations. As might be expected of agents that influence a large number of physiological functions, interferons produce numerous toxic side effects, some of which resemble those inflicted by viral diseases. These side effects are reversible and not life threatening.