Effects of recombinant human granulocyte colony-stimulating factor on neutrophil functions in aged animals

We have studied the effects of recombinant human granulocyte colony-stimulating factor (rG-CSF) on granulopoiesis and neutrophil functions in aged rats and aged mice. We subcutaneously injected rG-CSF or control vehicle into aged rats (22 months old and 25 months old) for 7 consecutive days, counted the peripheral neutrophils and evaluated the functions of neutrophils isolated from venous blood. The peripheral neutrophil count in aged rats tended to be increased as compared with that in young rats (11 weeks old). However, the neutrophils in aged rats exhibited a decline of superoxide anion (O2-) release and phagocytic activity as compared with young rats. The peripheral neutrophil count in aged rats was significantly increased 5-6-fold as many as the control value by rG-CSF treatment, which was accompanied by a significant enhancement of O2- release and of phagocytic activity being restored to normal levels or better. In another series of experiments, we subcutaneously injected rG-CSF or control vehicle into aged mice (24-28 months old) or young mice (8 weeks old) for 7 consecutive days, and evaluated the functions of neutrophils isolated from peritoneal cavity. The peritoneal exudate neutrophils from the aged mice exhibited a decline of phagocytic and chemotactic activity as compared with the young mice. These functions in both young and aged mice were significantly enhanced by rG-CSF-treatment, and these functions in rG-CSF-treated aged mice were restored to a level higher than the level in control young mice. These findings demonstrate that rG-CSF is capable of enhancing granulopoiesis and restoring the age-related decline of neutrophil functions.