Toxicity of Interferon

Abstract

Shortly after their discovery, interferons were found to have anti-viral and anti-proliferative activity. This led to the hope that they might have some role as therapeutic agents in the treatment of viral and neoplastic diseases. Early in vitro and in vivo work suggested that interferon was capable of causing lysis and death of cells in culture media (Nissen et al., 1977). Further in vivo testing in experimental animal systems soon showed that interferons exhibit a species specificity for both therapeutic and toxic effects (Gresser et al., 1981). In consequence, animal models (including primates) have not been capable of demonstrating all the toxicities exhibited when interferons have been used in human subjects. In addition, as different species of interferon have been isolated and purified for human use, it is becoming apparent that each specific type may have a different spectrum of activities and this includes unwanted toxic effects. It is therefore impossible to extrapolate from experience with one interferon to the effects of another interferon, even in similar clinical circumstances. It is also not yet known what effect, if any, the particular disease being treated has on the host response and susceptibility to the effects of interferon. This chapter aims to review some of the toxicities which appear to be common to all series so far reported and then to discuss in some detail the experience of one group using highly purified DNA recombinant interferon in advanced malignancy.