Ex vivo neutrophil function in response to three different doses of glycosylated rHuG-CSF (Lenograstim)

Granulocyte colony-stimulating factor (G-CSF) is being considered as adjuvant treatment for infections in non-neutropenic patients. Normal healthy donors were given rHuG-CSF (Lenograstim) at 2.5, 5.0 and 7.5 micrograms/kg subcutaneously daily for 5 d. Polymorphonuclear leucocyte (PMN) function tests were carried out on peripheral blood PMN before the first injection and at 24 h and 96 h. Circulating PMN levels were also measured at these time intervals and found to be significantly increased with all doses by 24 and 96 h. Investigation of cell surface antigen expression revealed no changes in beta 2 integrin (CD11b/ CD18) expression. L-selectin (CD62L) expression was reduced with all doses by 96 h, this being significant with the 7.5 micrograms/kg dose. Fc gamma RI (CD64) levels were significantly up-regulated with the 7.5 micrograms/kg dose by 96 h whereas Fc gamma RIII (CD16) expression was found to be reduced during G-CSF treatment. Superoxide anion production was significantly increased in response to N-formylmethionyl-leucylphenylalanine (FMLP) and opsonized Staphylococcus epidermidis stimulation at 24 h and 96 h with the 5.0 and 7.5 micrograms/kg doses. The initial rate of phagocytosis (0-2 min) appeared to have increased with the 7.5 and 5.0 micrograms/kg doses at 96 and 24 h compared with PMN responses pretreatment, although these increases were not statistically significant. These results show that G-CSF enhances the functional responses of PMN stimulated by physiological agnonists and may help in the treatment of infections.