Effect of Granulocyte-Colony Stimulating Factor on Generation of Oxygen-Derived Free Radicals and Myeloperoxidase Activity in Neutrophils From Poorly Controlled NIDDM Patients

To evaluate whether granulocyte-colony stimulating factor (G-CSF) improves an impaired production of oxygen-derived free radicals by neutrophils from poorly controlled NIDDM patients, we studied the effect of G-CSF on myeloperoxidase (MPO) activity and chemiluminescence amplified by a Cypridina luciferin analog (CLA-DCL), which is dependent on O⁻₂ generation, and luminol (L-DCL), which is dependent on OCl⁻ generation, in response to formyl-methonylleucyl- phenylalanine. Both CLA-DCL and L-DCL by neutrophils from the diabetic group (n = 15, HbA_1c >10%) were significantly decreased (26 and 37%, respectively: P < 0.01) compared with the age-matched normal control group (n = 15), and L-DCL was more sensitive to this inhibition than CLA-DCL (P > 0.05). In both control and diabetic neutrophils, G-CSF significantly enhanced both CLA-DCL (175% in control and 156% in diabetic) and L-DCL (283% in control and 346% in diabetic). In diabetic neutrophils, the enhancing effect of G-CSF on L-DCL was more sensitive than on CLA-DCL (P = 0.001). There was a positive correlation between HbA_lc and the enhancing effect of G-CSF on L-DCL in diabetic patients (P > 0.05), but not on CLA-DCL. MPO activity was also decreased in the diabetic group (63%, P > 0.05) , and G-CSF improved this impaired MPO activity (184%, P > 0.01). Furthermore, there was a positive correlation between HbA_1c and the improving effect of G-CSF on MPO activity (P > 0.05). Because bacterial infection still accounts for an important cause of morbidity and mortality in diabetic patients, these data suggest that G-CSF may be useful as a drug to prevent the aggravation of bacterial infection by improving neutrophil function, especially through H₂O₂-MPO-OCl⁻ mechanism, in poorly controlled diabetic patients.