Combination Protocols of Cytokine Therapy with Interleukin-3 and Granulocyte-Macrophage Colony-Stimulating Factor in a Primate Model of Radiation-Induced Marrow Aplasia
ARMED FORCES RADIOBIOLOGY RESEARCH INST BETHESDA MD
Pagination or Media Count:
Single cytokine therapy with granulocyte-macrophage colony- stimulating factor GM-CSF or interleukin-3 IL-3 has been shown to be effective in decreasing the respective periods of neutropenia and thrombocytopenia following radiation- or drug-induced marrow aplasia. The combined administration of IL-3 and GM-CSF in normal primates suggested that a sequential protocol of IL-3 followed by GM-CSF would be more effective than that of GM-CSF alone in producing neutrophils PMN. We investigated the therapeutic efficacy of two combination protocols, the sequential and co-administration of recombinant human IL-3 and GM-CSF relative to respective single cytokine therapy, and delayed GM-CSF administration in sublethally irradiated rhesus monkeys. Monkeys irradiated with 450 cGy mixed fission neutrongamma radiation received either IL-3, GM-CSF, human serum albumin HSA, or IL-3 co-administered with GM-CSF for days 1 through 21 consecutively postexposure, or IL-3 or HSA for days 1 through 7 followed by GM-CSF for days 7 through 21. All cytokines and HSA were injected subcutaneously at a total dose of 25 mircogramskgd, divided twice daily. Complete blood counts CBC and platelet PLT counts were monitored over 60 days postirradiation.
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