Safety evaluation of recombinant human interleukin-4. I. Preclinical studies.
Recombinant human IL-4 (rhuIL-4) has been evaluated in a series of preclinical studies. These studies have demonstrated that rhuIL-4 is a very potent cytokine with a wide range of pharmacologic and toxicologic effects. Target systems/organs included the cardiovascular system, liver, spleen, and bone marrow. The incidence and severity of effects correlated 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 necrosis and occurred at sc doses > or = 25 micrograms/kg/day, while a sc dose of 5 micrograms/kg/day was the highest tested that did not result in major dose-limiting toxicity. Clinical trials in humans have demonstrated that sc administration of Escherichia coli-derived rhuIL-4 is safe and well tolerated at doses up to and including 5 micrograms/kg/day and up to 10 micrograms/kg when administered 3 times/week.
Leach
M W
MW
Schering-Plough Research Institute, Lafayette, New Jersey 07848, USA.
Snyder
E A
EA
Sinha
D P
DP
Rosenblum
I Y
IY
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004926:Escherichia coli / Q000378:metabolism; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology* / Q000592:standards* / Q000633:toxicity; D011994:Recombinant Proteins / Q000494:pharmacology / Q000592:standards / Q000633:toxicity
D011994:Recombinant Proteins; D015847:Interleukin-4