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In vivo effects of interleukin-6 on thrombopoiesis in healthy and
irradiated primates [see comments]
C Zeidler, L Kanz, F Hurkuck, KL Rittmann, I Wildfang, T Kadoya, T Mikayama, L Souza and K Welte
Department of Pediatric Hematology and Oncology, Medical School Hannover,
Germany.
We have studied the in vivo effects of recombinant human interleukin-6
(rhIL-6) on hematopoiesis in eight healthy and nine irradiated cynomolgus
monkeys. Of the healthy animals, three received rhIL-6 alone (10
micrograms/kg/d, subcutaneously [SC]), one received rhIL-6 in combination
with rhIL-3 (10 micrograms/kg/d, SC), one received rhIL-6 in combination
with recombinant cynomolgus granulocyte-macrophage colony-stimulating
factor (rcGM-CSF; 10 micrograms/kg/d, SC), two received rhIL-6 in
combination with recombinant human granulocyte-CSF (rhG-CSF; 10
micrograms/kg/d, SC), and one received rhIL-6 in combination with
recombinant human leukemia inhibitory factor (rhLIF; 10 micrograms/kg/d,
SC). All animals were treated for at least 2 weeks with rhIL-6 or the above
mentioned combinations. rhIL-6 alone significantly increased the peripheral
blood platelet counts (2- to 3.5- fold). The platelets reached a plateau
between days 10 and 15 of treatment. No synergistic effects on platelet
numbers were observed when rhIL-6 was combined with rhIL-3, rcGM-CSF,
rhG-CSF, or rhLIF. In addition to rhIL-6, only rhLIF increased the platelet
numbers when administered alone. To test whether rhIL-6 might also protect
the animal from thrombocytopenia or shorten the time of thrombocytopenia
after irradiation, we treated nine animals with total body irradiation (3.8
Gy). Six of the animals were additional treated with rhIL-6 (4 with 10
micrograms/kg/d; and 2 with 100 micrograms/kg/d) from day -1 or +1 to day
28 post irradiation. In these animals, rhIL-6 at the same dose effective in
healthy animals (10 micrograms/kg/d) was not capable of protecting the
animals from platelet nadir. However, when pegylated rhIL-6 was used at a
dosage of 100 micrograms/kg/d post irradiation, the mean of the nadirs was
71,000/microL as compared with 39,000/microL in control animals and the
time of thrombocytopenia was shorter (3 v 5 days). In all animals (healthy
and irradiated), rhIL-6 did not increase the number of bone marrow
megakaryocytes but induced a right shift of DNA ploidy in megakaryocytes.
These data suggest that IL-6 acts as "thrombopoietin"-like activity, but
not as "megakaryocyte-CSF"-like activity.
Volume 80,
Issue 11,
pp. 2740-2745,
12/01/1992
Copyright © 1992 by The American Society of Hematology
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