Pharmacology of interferons I. pharmacologic distinctions between human leukocyte and fibroblast interferons

Abstract

Human leukocyte and fibroblast interferons were inoculated into rabbits and mice by various routes to determine their survival in circulation and their distributions in body tissues. Human leukocyte interferon inoculated intraperitoneally, intramuscularly, subcutaneously or intravenously was found to enter the circulation efficiently and was widely distributed in the tissues for several hours. However, human fibroblast interferon entered the blood inefficiently; human fibroblast interferon was only transiently detectable in the circulation and at significantly lower levels than the leukocyte interferon and could never be detected in any of the solid tissues. When these interferons were incubated with various body fluids from mice, rabbits or humans, both interferons had similar stabilities in blood and in cerebrospinal fluid, while fibroblast interferon was less stable than leukocyte interferon in urine. A marked distinction was found between the stabilities of the two human interferons in muscle tissue: human leukocyte interferon was completely stable in tissue homogenates prepared from mouse, rabbit or human muscles, whereas fibroblast interferon was rapidly inactivated by such suspensions. Human fibroblast interferon was also rapidly destroyed by a cell-free extract prepared from either human, mouse or rabbit muscle tissues. These data demonstrate that human leukocyte interferon has pharmacologically advantageous properties which allow it to enter efficiently into the circulation following intramuscular injection and to distribute to the body tissues, whereas human fibroblast interferon is unable to do so because the latter is inactivated by the tissues at the site of inoculation. Thus, for therapeutic exploitation, human fibroblast interferon may be limited to topical administration only, whereas human leukocyte interferon would be much preferred for systemic use.