CHRONIC NEUTROPENIA AND DEFECT IN SUPEROXIDE GENERATION OF GRANULOCYTES IN 2 PATIENTS - ENHANCEMENT OF BACTERICIDAL CAPACITY AND RESPIRATORY BURST ACTIVITY BY TREATMENT WITH RECOMBINANT HUMAN GRANULOCYTE-COLONY-STIMULATING FACTOR

We have identified two unrelated girls with chronic neutropenia [absol ute neutrophil counts (ANC) 10-870 and 10-940/mu L in patients 1 and 2 , respectively] and severe defect in superoxide anion generation by gr anulocytes. Formyl-methionyl-leucyl-phenylalanine-induced superoxide r elease was 1.2 +/- 0.9 and 1.9 +/- 1.9% (mean +/- SEM, n = 3) of norma l controls', mean value in patients 1 and 2, respectively. However, gr anulocytes from both patients released a normal amount of superoxide u pon stimulation with phorbol myristate acetate. Patient 2 exhibited ch aracteristic features of Duane syndrome, a rare disorder of eye moveme nt. Treatment of the patients with recombinant granulocyte colony-stim ulating factor led to significant clinical improvements and reduction of infectious complications and to increases in the ANC, to 400-2100/m u L in patient 1 and to 500-3000/mu L in patient 2, Treatment with 5 m u g/kg/d resulted in increased intracellular killing of opsonized Stap hylococcus aureus by granulocytes and an enhancement of superoxide rel ease upon stimulation with formyl-methionyl-leucyl-phenylalanine in bo th patients up to 11.1 +/- 6.0 and 13.5 +/- 7.0% (mean +/- SEM, n = 5) of normal controls', mean value in patient 1 and patient 2, respectiv ely. These data suggested that recombinant human granulocyte colony-st imulating factor treatment enhanced resistance to bacterial infection by stimulation of superoxide generation and increasing the bactericida l capacity of peripheral blood granulocytes.