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The in vivo effects of recombinant human interleukin-3: demonstration of
basophil differentiation factor, histamine-producing activity, and priming
of GM-CSF-responsive progenitors in nonhuman primates
P Mayer, P Valent, G Schmidt, E Liehl and P Bettelheim
Sandoz Research Center, Vienna, Austria.
Recently human interleukin-3 (IL-3) produced by molecular cloning was
characterized as a growth factor for basophils and eosinophils in human
bone marrow cultures. Since we found a similar activity of the human factor
on simian bone marrow cells, we investigated the in vivo effects of
recombinant human (rh) IL-3 in healthy rhesus monkeys (n = 10). rh IL-3 was
administered subcutaneously (SC) to monkeys at different doses (11, 33, and
100 micrograms/kg/d) for 14 days followed by subsequent rh GM-CSF
administration (5.5 micrograms/kg/d SC) for another two weeks. During the
second week of rh IL-3 administration monkeys responded with a twofold to
threefold increase of WBCs caused by a dose-dependent elevation of
basophils (up to 40% of WBCs) and eosinophils. rh IL-3 also induced a
dose-dependent increase of histamine (up to 700-fold above normal values)
in monkey blood cells. Administration of rh GM-CSF to rh IL-3 pretreated
monkeys resulted in a twofold enhanced increase in WBCs (due mainly to
eosinophils and neutrophils) compared with animals treated with rh GM-CSF
alone. Simultaneous administration of both cytokines (100 micrograms/kg rh
IL-3 + 5.5 micrograms/kg rh GM-CSF SC) to two separate monkeys for 14 days
induced a WBC elevation similar to that observed in monkeys treated with rh
GM-CSF alone. In conclusion, our results indicate that rh IL-3 is a
differentiation factor for blood basophils and primes the hematopoietic
system for subsequent rh GM-CSF actions.
Volume 74,
Issue 2,
pp. 613-621,
08/01/1989
Copyright © 1989 by The American Society of Hematology
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