In vivo synergism of recombinant human interleukin-3 and recombinant human interleukin-6 on thrombopoiesis in primates.
Using a primate model, we examined the effect of recombinant human interleukin-3 (rhIL-3) and rhIL-6 on thrombopoiesis in vivo. Administration of 33 micrograms/kg/d of rhIL-3 for 11 to 14 days increased levels of circulating colony-forming units megakaryocyte (CFU-Mk) by approximately 15-fold in five rhesus monkeys without raising their platelet counts. In contrast, administration of 30 micrograms/kg/d of rhIL-6 for 10 days in four animals did not increase CFU-Mk levels but significantly raised platelet counts from a mean pretreatment value of 460 x 10(3)/microL (range 360 to 610) to a mean maximum of 746 x 10(3)/microL (665 to 790) on day 8. If monkeys were pretreated with rhIL-3 (33 or 100 micrograms/kg/d for 11 days) to expand their CFU-Mk compartment, the thrombopoietic effect of rhIL-6 was synergistically enhanced leading to platelet counts above 1,000 x 10(3)/microL (mean maximum value 1,247) in all three primates studied. The sequential administration of rhIL-3 and rhIL-6 might represent a powerful strategy to stimulate thrombopoiesis in vivo.
Geissler
K
K
First Department of Medicine, University of Vienna, Austria.
Valent
P
P
Bettelheim
P
P
Sillaber
C
C
Wagner
B
B
Kyrle
P
P
Hinterberger
W
W
Lechner
K
K
Liehl
E
E
Mayer
P
P
D000818:Animals; D003114:Colony-Forming Units Assay; D004357:Drug Synergism; D004906:Erythrocyte Count; D006410:Hematopoiesis; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology*; D007958:Leukocyte Count; D008253:Macaca mulatta / Q000097:blood; D008533:Megakaryocytes / Q000166:cytology*; D010976:Platelet Count; D011994:Recombinant Proteins / Q000494:pharmacology
D007377:Interleukin-3; D015850:Interleukin-6; D011994:Recombinant Proteins