Reduced Hydrogen Peroxide Production in Neutrophils from Patients with Diabetes

We evaluated the effects of granulocyte colony-stimulating factors (G-CSF), granulocyte-macrophage colony-stimulating factors (GM-CSF) and phorbol myristate acetate (PMA) on H2O2 production in purified neutrophils from patients with diabetes mellitus (DM), using flow cytometry. Twenty-two age-matched male subjects were selected: 11 were normal volunteers and the remainder had DM. No significant differences in intracellular H2O2 production per 60 min was observed in the "resting' neutrophils from DM patients (37.2 +/- 20.4 A.U.) compared with those from normal volunteers (24.9 +/- 8.4 A.U.). The PMA-stimulated neutrophils from normal volunteers generated approximately 4-fold increases in H2O2 per 60 min compared with those from DM patients. Under similar culture conditions, G-CSF caused 1.6-fold increases of H2O2 in neutrophils from normal volunteers compared with those of DM patients. Increases after GM-CSF stimulation were 2-fold higher in volunteer neutrophils compared with those from DM patients. The levels of G-CSF- or GM-CSF-stimulated H2O2 production in neutrophils from DM patients were low and were little different from non-stimulated resting cells. These data showed that H2O2 production in neutrophils induced by PMA is impaired in patients with DM, and neither G-CSF nor GM-CSF enhances its production.