Clinical Pathologic Alterations Associated with Subcutaneous Administration of Recombinant Human Interleukin-4 to Cynomolgus Monkeys

Recombinant human interleukin 4 (rhuIL-4) is a candidate for the treatment of refractory cancer based on its potential to enhance immune function. Recombinant human IL-4 was administered subcutaneously at 0, 1, 5, or 25 μg/kg/day for 28 days with a 14-day recovery to male and female cynomolgus monkeys as part of the preclinical safety evaluation. Clinical pathologic changes related to treatment with rhuIL-4 were evidence of consumptive coagulopathy, erythrocyte fragmentation, lymphocytosis, and lymphocyte morphologic changes indicative of marked antigenic or mitogenic stimulation, mild eosinophilia and neutrophilia, hypoalbuminemia, hypocholesterolemia, and hypertriglyceridemia. Based on data obtained after the 14-day recovery period, the clinical pathologic changes associated with rhuIL-4 administration were considered to be reversible.