Histomorphologic observations for cynomolgus monkeys after subchronic subcutaneous injection of recombinant human interleukin-4.
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 micrograms/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 micrograms/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 micrograms/kg/day groups at 1 month and after 2 weeks of recovery.
Barbolt
T A
TA
Department of Toxicology, Sterling Research Group, Rensselaer, New York 12144.
Gossett
K A
KA
Cornacoff
J B
JB
D000818:Animals; D001808:Blood Vessels / Q000166:cytology / Q000187:drug effects; D005260:Female; D005837:Genitalia, Male / Q000166:cytology / Q000187:drug effects; D006413:Hematopoietic System / Q000166:cytology / Q000187:drug effects; D006801:Humans; D015847:Interleukin-4 / Q000008:administration & dosage*; D008221:Lymphoid Tissue / Q000166:cytology / Q000187:drug effects; D008252:Macaca fascicularis; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects; D011994:Recombinant Proteins / Q000008:administration & dosage; D014652:Vascular Diseases / Q000139:chemically induced / Q000473:pathology
D011994:Recombinant Proteins; D015847:Interleukin-4