SAFETY EVALUATION OF RECOMBINANT HUMAN INTERLEUKIN-4 .1. PRECLINICAL STUDIES

Recombinant human IL-4 (rhuIL-4) has been evaluated in a series of pre clinical studies. These studies have demonstrated that rhuIL-4 is a ve ry potent cytokine with a wide range of pharmacologic and toxicologic effects. Target systems/organs included the cardiovascular system, liv er, spleen, and bone marrow, The incidence and severity of effects cor related strongly with both the dose level and the duration of rhuIL-4 administration. The major dose-limiting toxicities identified included death, cardiac inflammation and necrosis, hepatitis, and hepatic necr osis and occurred at sc doses greater than or equal to 25 mu g/kg/day, while a sc dose of 5 mu g/kg/day was the big-best tested that did not result in major dose-limiting toxicity. Clinical trials in humans hav e demonstrated that sc administration of Escherichia, call-derived rhu IL-4 is safe and well tolerated at doses up to and including 5 mu g/kg /day and up to 10 mu g/kg when administered 3 times/week. (C) 1997 Aca demic Press.