Effect of N‐methionine‐free, bacterially synthesized recombinant human granulocyte‐macrophage colony‐stimulating Factor in a primate model

Abstract: We demonstrate the in vivo effects of bacterially synthesized, N‐methionine‐free recombinant human granulocyte‐macrophage colony stimulating factor (rh GM‐CSF) using a crab‐eating monkey model. Monkeys were treated with cyclophosphamide (60 mg/kg) and administered with rh GM‐CSF (30 μg/kg/d) subcutaneously (s.c.) for 7 days. Within 12 h, a transient increase of neutrophils (> 15.0 × 10⁹/l) was observed, and complete recovery of WBC counts was obtained by d 9 (d 16 in control monkeys). Neutrophils and eosinophils were absolutely increased (>8 × 10⁹/l) on d 10. Readministration of rh GM‐CSF (30 μg/kg/d, s.c.) for 3 d (including control monkeys) revealed absolute increases of neutrophils, eosinophils, monocytes and platelets. A two‐fold increase of granulocyte/macrophage colony‐forming units was also seen in the bone marrow, while the number of burst‐forming units‐erythroid was not affected. These data indicate that rh GM‐CSF of this type stimulates granulopoiesis and thrombopoiesis in vivo.