Histomorphologic Observations for Cynomolgus Monkeys after Subchronic Subcutaneous Injection of Recombinant Human Interleukin-4

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Abstract
Recombinant human interleukin-4 (rhuIL-4) is a candidate for the treatment of refractory cancer based on its potential to enhance the function of the immune system. Total daily dosages of 0 (placebo control), 1,5, or 25 μg/kg of rhuIL-4 were given as divided (b.i.d.) subcutaneous dosages to male and female cynomolgus monkeys (5/sex/group) for 1 month followed by a 2-week recovery. Histomorphologic evaluation of 3/sex/group at 1 month revealed vascular lesions, granulocytic hyperplasia, and seminiferous tubular atrophy attributed to treatment with rhuIL-4. Dosage-dependent proliferative and inflammatory vascular lesions with eosinophil infiltration affected principally the arterial tree. After 2 weeks of recovery, these lesions, including chronic endarteritis and chronic and/or obliterative arteritis, occurred with an overall lower incidence, and were not observed for monkeys from the 1.0 μg/kg/day group. Granulocytic hyperplasia in bone marrow observed for monkeys from all groups given rhuIL-4 at 1 month was not present after 2 weeks of recovery. Seminiferous tubular atrophy was observed for monkeys from the 5 and 25 μg/kg/day groups at 1 month and after 2 weeks of recovery.