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Histomorphologic Observations for Cynomolgus Monkeys after Subchronic Subcutaneous Injection of Recombinant Human Interleukin-4
Thomas A. Barbolt
Department of Toxicology, Sterling Research Group, Rensselaer, New York 12144
Kent A. Gossett
Department of Toxicology, Sterling Research Group, Rensselaer, New York 12144
Joel B. Cornacoff
Department of Toxicology, Sterling Research Group, Rensselaer, New York 12144
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.
Key Words: Arteritis • eosinophil infiltration • smooth muscle cell proliferation • granulopoiesis • lymphoid depletion • seminiferous tubular atrophy
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Toxicologic Pathology, Vol. 19, No. 3,
251-257 (1991)
DOI: 10.1177/019262339101900307
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K. A. Gossett, T. A. Barbolt, J. B. Cornacoff, D. J. Zelinger, and J. H. Dean
Clinical Pathologic Alterations Associated with Subcutaneous Administration of Recombinant Human Interleukin-4 to Cynomolgus Monkeys
Toxicol Pathol,
January 1, 1993;
21(1):
46 - 53.
[Abstract]
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