Recombinant granulocyte colony-stimulating factor induces production of human neutrophil peptides in lung cancer patients with neutropenia

Abstract

Human neutrophil peptides (HNPs) 1, 2 and 3 are antimicrobial peptides localized in the azurophil granules of neutrophils. We investigated the effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on the biosynthesis of HNPs 1–3 using a sensitive radioimmunoassay and Northern blot analysis. Seven patients with lung cancer were first treated with various anticancer agents for 3 days (days 1–3) followed by treatment with rhG-CSF (2 μg/kg weight/day) for 7 days (days 8–14). Chemotherapy caused neutropenia but the neutrophil count increased biphasically between days 8 and 14. Chemotherapy did not change the baseline plasma concentration of HNPs 1–3 (74.1±2.1 pmol/ml) but the concentration increased from day 12, 5 days after commencement of rhG-CSF therapy, to reach a peak value of 430.8±57.0 pmol/ml on day 15, 1 day after the last administration of rhG-CSF. Baseline HNPs 1–3 content per neutrophil was 0.59±0.02 fmol, decreased to 0.30±0.07 fmol on day 9, then increased to 0.78±0.07 fmol on day 15. Analyses of peripheral blood neutrophils by Northern blot and reverse-phase high-performance liquid chromatography showed that the amounts of HNPs 1–3 mRNA and precursors of HNPs 1–3 markedly increased in response to rhG-CSF. Our results indicate that recombinant hG-CSF does not only increase neutrophil count but stimulates HNPs 1–3 biosynthesis in neutrophils, thus enhancing the host defense system of compromised hosts with neutropenia.