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Thrombocytopoiesis in normal and sublethally irradiated dogs: response to
human interleukin-6
SA Burstein, T Downs, P Friese, S Lynam, S Anderson, J Henthorn, RB Epstein and K Savage
Department of Medicine, University of Oklahoma Health Sciences Center,
Oklahoma City 73190.
The response of megakaryocytes and platelets to the administration of
recombinant human interleukin-6 (IL-6) was investigated in normal and
sublethally irradiated dogs. IL-6 was administered for 2 weeks at doses of
10 to 160 micrograms/kg/d to normal animals to assess dose-response and
toxicity. Subsequently, 40, 80, or 160 micrograms/kg/d for 2 weeks was
administered to animals treated with 200 cG total body irradiation.
Analysis of normal dogs showed a significant increment in the platelet
count detectable approximately 11 days after initiation of IL-6 at all
administered doses. Large platelets greater than 6.3 microns in diameter
were observed 1 day after beginning IL-6, progressively increasing to as
many as 19.1% of the total circulating platelets by day 10. The ploidy
distribution of the marrow megakaryocytes did not differ from the normal at
doses of less than or equal to 80 micrograms/kg/d, but at 160
micrograms/kg/d, a shift toward higher ploidy cells was noted. No change in
total white count was noted; however, a decrease in hematocrit was seen at
all doses. In the irradiated animals, the platelet count recovered earlier
in the IL-6- treated dogs than in the controls, but no consistent change in
the ploidy distribution was observed irrespective of dose. Large platelets
were also noted in the treated animals, comprising up to 6.9% of the total
platelet count. Fibrinogen levels were elevated to greater than 4 times
normal. A significant decrease in hematocrit was seen in all animals, while
no consistent change was noted in the white count. Elevations in serum
cholesterol, triglycerides, and alkaline phosphatase, together with a
decline in serum albumin were observed in all the treated animals (both
normal and irradiated), but clinical symptoms were observed only in the
dogs receiving greater than or equal to 80 micrograms/kg/d. The data show
that IL-6 alone is capable of enhancing platelet recovery in dogs with bone
marrow suppression.
Volume 80,
Issue 2,
pp. 420-428,
07/15/1992
Copyright © 1992 by The American Society of Hematology
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