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Enhancement of the biologic effects of interleukin-3 in vivo by anti-
interleukin-3 antibodies
AT Jones and HJ Ziltener
Biomedical Research Centre, University of British Columbia, Vancouver,
Canada.
Interleukin-3 (IL-3) has been shown to be a promising agent in the
stimulation of bone marrow regeneration following myeloablative therapy.
The biologic half-life of this agent is very short (5 to 15 minutes), which
limits the effectiveness of low-dose therapy. Here we show that the
biologic effects of low-dose IL-3 in mice may be enhanced by concurrent use
of polyclonal anti-IL-3 antibodies. The biologic effects of IL-3 in vivo
were enhanced dramatically by the combination of the cytokine and
polyclonal rabbit anti-IL-3 antibodies, which recognized a peptide
comprising the first 29 amino acids of the IL-3 molecule. Enhancing effects
were not apparent in vitro, where weak neutralizing properties were
observed for these antibodies. The mechanism of this enhancement by the
antibody appears to be via a ninefold reduction in the total-body clearance
of the cytokine in vivo. The apparent volumes of distribution for IL-3 and
for the IL-3/antibody complex were surprisingly similar and exceeded the
expected intravascular volume. The prolonged biologic half-life of IL-3 was
reproducibly associated with a threefold to fivefold increase in splenic
mast-cell precursors over levels observed in mice treated with IL-3 alone;
increases in the numbers of mature mucosal-type mast cells in the spleen,
but not in the jejunum or lung; increases in IL-3- dependent colony-forming
unit-cell in the spleen; and an apparent redistribution of mast cells away
from the bone marrow. These experiments demonstrate that antibodies to a
cytokine can enhance the biologic activity of that cytokine in vivo.
Volume 82,
Issue 4,
pp. 1133-1141,
08/15/1993
Copyright © 1993 by The American Society of Hematology
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