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Therapeutic efficacy of recombinant interleukin-6 (IL-6) alone and combined
with recombinant human IL-3 in a nonhuman primate model of high-dose,
sublethal radiation-induced marrow aplasia
TJ MacVittie, AM Farese, ML Patchen and LA Myers
Armed Forces Radiobiology Research Institute, Bethesda, MD 20889-5603.
Using a nonhuman-primate model of radiation-induced bone marrow aplasia, we
examined whether the single, concomitant, or sequential administration of
recombinant human interleukin-3 (IL-3) and IL-6 would promote bone marrow
regeneration measured by an increase in circulating platelets (PLT) and
neutrophils (PMN). Rhesus monkeys were irradiated at 450 cGy and were
randomly assigned to one of five treatment protocols, receiving IL-6; IL-3;
combined IL-6 and IL-3; sequential IL- 3 and IL-6; or human serum albumin
(HSA) as a control. Cytokines or HSA were administered at total dosages of
15 micrograms/kg/day. Complete blood counts and white blood cell
differentials were monitored for 60 days postirradiation. Both IL-3 and
IL-6 significantly enhanced the regeneration of PLTs and decreased the
duration of thrombocytopenia (P = .005) without affecting PMN recovery. The
radiation-induced anemia that was observed in the HSA-treated controls was
less severe and resolved more quickly in the IL-6 treated animals.
Sequential IL-3/IL-6 significantly increased the production of PLTs when
compared with the HSA-treated controls (P = .003) and monkeys receiving
concomitant IL- 3/IL-6 (P = .041) but did not alter PMN levels
significantly (P = .80). Coadministration of IL-6 and IL-3 did not enhance
PLT but improved PMN recovery over IL-6 alone. In this primate model of
marrow aplasia, IL-6 significantly enhanced the regeneration of PLTs but
had no significant effect on PMN production, and did not exacerbate
radiation-induced anemia. Furthermore, the use of sequentially administered
IL-3 and IL-6 may improve PLT recovery as compared with concurrent
IL-3/IL-6 administration, although this protocol is not significantly
different in effect than either cytokine alone.
Volume 84,
Issue 8,
pp. 2515-2522,
10/15/1994
Copyright © 1994 by The American Society of Hematology

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