Multiple effects on peripheral hematology following administration of recombinant human interleukin 12 to nonhuman primates.
Interleukin 12 has demonstrated a wide spectrum of bioactivity on T and NK cells both in vitro and in vivo. Therapeutic potential of these activities has been suggested by studies in murine tumor, viral and microbial models of disease. We have investigated the in vivo effect of rhlL-12 in cynomolgus monkeys treated with 1 micrograms/kg/day by bolus i.v. or s.c. injection for 5 days. Treated group transient decreases in total WBC counts as compared to controls, with reversable decreases seen mainly in the lymphocyte and monocyte subsets. Phenotypic analysis showed a decrease in the number of CD4+ and CD8+ cells/microL on Days 2 and 4. Reversible thrombocytopenia and anemia were noted in both treated groups as compared to controls. Plasma neopterin concentrations were increased in both treated groups as compared to controls. These data show that rhlL-12 has multiple effects on peripheral hematology and suggests that this model may be useful to investigate in vivo bioactivity of rhlL-12.
Genetics Institute, Inc., Cambridge, Massachusetts.
A G
AG
Bree
F J
FJ
Schlerman
M D
MD
Kaviani
R C
RC
Hastings
S L
SL
Hitz
S J
SJ
Goldman
D000818:Animals; D001708:Biopterins / Q000031:analogs & derivatives / Q000097:blood; D006400:Hematocrit; D016130:Immunophenotyping; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D018664:Interleukin-12 / Q000008:administration & dosage / Q000494:pharmacology*; D007958:Leukocyte Count / Q000187:drug effects*; D018655:Lymphocyte Count / Q000187:drug effects; D016131:Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology*; D008252:Macaca fascicularis; D008297:Male; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D019798:Neopterin; D010976:Platelet Count / Q000187:drug effects*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D012016:Reference Values; D013997:Time Factors
D011994:Recombinant Proteins; D018664:Interleukin-12; D001708:Biopterins; D019798:Neopterin