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Administration of interleukin-6 stimulates multilineage hematopoiesis and
accelerates recovery from radiation-induced hematopoietic depression
ML Patchen, TJ MacVittie, JL Williams, GN Schwartz and LM Souza
Department of Experimental Hematology, Armed Forces Radiobiology Research
Institute, Bethesda, MD 20889-5145.
Hematopoietic depression and subsequent susceptibility to potentially
lethal opportunistic infections are well-documented phenomena following
radiotherapy. Methods to therapeutically mitigate radiation-induced
myelosuppression could offer great clinical value. In vivo studies in our
laboratory have demonstrated that interleukin-6 (IL-6) stimulates
pluripotent hematopoietic stem cell (CFU-s), granulocyte-macrophage
progenitor cell (GM-CFC), and erythroid progenitor cell (CFU-e)
proliferation in normal mice. Based on these results, the ability of IL- 6
to stimulate hematopoietic regeneration following radiation-induced
hematopoietic injury was also evaluated. C3H/HeN female mice were exposed
to 6.5 Gy 60Co radiation and subcutaneously administered either saline or
IL-6 (1,000 micrograms/kg) on days 1 through 3 or 1 through 6 postexposure.
On days 7, 10, 14, 17, and 22, femoral and splenic CFU-s, GM-CFC, and CFU-e
contents and peripheral blood white cell, red cell, and platelet counts
were determined. Compared with saline treatment, both 3-day and 6-day IL-6
treatments accelerated hematopoietic recovery; 6-day treatment produced the
greater effects. For example, compared with normal control values (N),
femoral and splenic CFU-s numbers in IL-6-treated mice 17 days
postirradiation were 27% N and 136% N versus 2% N and 10% N in
saline-treated mice. At the same time, bone marrow and splenic GM-CFC
values were 58% N and 473% N versus 6% N and 196% N in saline-treated mice;
bone marrow and splenic CFU-e numbers were 91% N and 250% N versus 31% N
and 130% N in saline-treated mice; and peripheral blood white cell, red
cell, and platelet values were 210% N, 60% N, and 24% N versus 18% N, 39%
N, and 7% N in saline- treated mice. These studies demonstrate that
therapeutically administered IL-6 can effectively accelerate multilineage
hematopoietic recovery following radiation-induced hematopoietic injury.
Volume 77,
Issue 3,
pp. 472-480,
02/01/1991
Copyright © 1991 by The American Society of Hematology
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