A Phase I Trial of Immune Interferon

A variety of interferons have now been tested in clinical trials. Most of these trials have utilized leukocyte (α) interferon preparations. Early trials were conducted with partially purified material derived from the supernatants of virus-stimulated leukocytes that were of low purity and inconsistent pharmaceutical quality. More recently, trials have been conducted with a lymphoblastoid cell line interferon (α) of high purity and good reproducibility (Knost et al., 1983). Several recent studies have utilized recombinant α-interferon derived by cloning a gene for α-interferon in an E. coli expression system (Sherwin et al., 1982, 1983). Despite the major differences between these α-interferon preparations, many of the toxicities, immunological modulating effects, and therapeutic effects have been similar. Fever, chills, headache, fatigue, and anorexia have been rather constant side effects of these interferon preparations. At higher doses, mild hematological depression and transient hepatic enzyme abnormalities have been seen. Occasional cardiac effects including arrhythmias and ischemic effects have been observed in the context of these trials. Some central nervous toxicity including confusion, decreased ability to concentrate, and rarely seizures at very high doses have been seen in these studies. It is unclear whether all these effects are due to the direct action of the interferon preparation since the induction of fever, tachycardia, and fatigue may have secondary effects (Oldham, 1983a). The phase I trials for the α-interferons are virtually complete.