In vivo effects of recombinant human granulocyte colony-stimulating factor on normal neutrophil function and membrane effector molecule expression.

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) is now undergoing clinical trials. We investigated the effects of rhG-CSF on the function of neutrophils in vivo in healthy volunteers. rhG-CSF (0.5 micrograms/kg) was injected subcutaneously for 6 consecutive days. The number of neutrophils in peripheral blood decreased transiently within an hour, and thereafter increased 2-10-fold compared to the control 6 to 8 h after injection. The circulating neutrophils remaining during this early neutropenic period showed increases in such functions as random motility, chemotaxis, phagocytosis and superoxide anion production. On the other hand, the function of neutrophils which increased 6 to 8 h after rhG-CSF injection was normal. No decrease of neutrophil function was observed following the use of rhG-CSF. CD33-positive cells increased 3 days after rhG-CSF administration. CD11a (LFA-1) expression on the membranes circulating neutrophils decreased 6 h after rhG-CSF administration. This phenomenon suggested that neutrophils adhered to the reticuloendothelial system during neutropenia, and that there was an influx of CD11a-negative mature cells into the circulatory pool thereafter. All our findings suggest that rhG-CSF enhances the function of normal neutrophils in vivo, and that it is effective against microbial infection very soon after administration.