Thrombopoietic activity of recombinant human interleukin 11 (rHuIL-11) in normal and myelosuppressed nonhuman primates.
We have extensively characterized the hematological response of normal and myelosuppressed nonhuman primates to treatment with recombinant human interleukin 11 (rHuIL-11) in vivo. In normal cynomolgus monkeys, rHuIL-11 significantly increased peripheral platelet counts when administered at doses of 10 micrograms/kg/day to 100 micrograms/kg/day either by constant i.v. infusion or s.c. injection. As few as four days of rHuIL-11 treatment were sufficient to increase peripheral platelet counts significantly. In addition, extending the treatment period enhanced both the magnitude and the duration of the response. Bone marrow megakaryocytes from animals treated with 100 micrograms/kg/day of rHuIL-11 were increased in size compared to controls and were ultrastructurally normal. A nonhuman primate myelosuppression model using carboplatin, which causes severe thrombocytopenia with platelet counts of < or = 20 x 10(3) platelets/microliters, was developed. This novel model was used to evaluate the effectiveness of rHuIL-11 in platelet restoration. rHuIL-11, administered s.c. at a dose of 125 micrograms/kg/day either concurrently or following chemotherapy, prevented severe thrombocytopenia in addition to accelerating platelet recovery compared to control animals receiving no rHuIL-11. These data demonstrate that rHuIL-11 has potent in vivo thrombopoietic effects when administered to normal and myelosuppressed nonhuman primates, and that rHuIL-11 can be an important therapy to reduce the severity and duration of thrombocytopenia following chemotherapy.
Genetics Institute, Inc., Cambridge, Massachusetts, USA.
F J
FJ
Schlerman
A G
AG
Bree
M D
MD
Kaviani
S L
SL
Nagle
L H
LH
Donnelly
L E
LE
Mason
R G
RG
Schaub
S A
SA
Grupp
S J
SJ
Goldman
D000818:Animals; D001792:Blood Platelets / Q000166:cytology / Q000378:metabolism*; D001798:Blood Proteins / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006410:Hematopoiesis / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006801:Humans; D007165:Immunosuppression Therapy; D017370:Interleukin-11 / Q000494:pharmacology*; D007958:Leukocyte Count / Q000187:drug effects; D008252:Macaca fascicularis; D008297:Male; D008533:Megakaryocytes / Q000166:cytology / Q000378:metabolism; D010976:Platelet Count / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology; D012156:Reticulocytes / Q000166:cytology / Q000187:drug effects
D001798:Blood Proteins; D017370:Interleukin-11; D011994:Recombinant Proteins