PROTECTION OF HUMAN POLYMORPHONUCLEAR LEUKOCYTE FUNCTION FROM THE DELETERIOUS EFFECTS OF ISOLATION, IRRADIATION, AND STORAGE BY INTERFERON-GAMMA AND GRANULOCYTE-COLONY-STIMULATING FACTOR

Background: Fungal infections represent a difficult challenge to clini cians caring for neutropenic patients with hematologic malignancies, a s antifungal therapy often has limited success in that setting, One pr omising yet problematic alternative approach is leukocyte transfusion. The isolation of polymorphonuclear leukocytes (PMNs) induces apoptosi s and functional deterioration, and irradiation to prevent transfusion -associated graft-versus-host disease causes further functional deteri oration. Study Design and Methods: The ability of interferon-gamma and granulocyte-colony stimulating factor (G-CSF), used both alone and in combination, to protect PMNs after 0 or 20 hours' storage in cell cul ture (as a model for function after transfusion) and irradiation with 0, 5, or 30 Gy was studied. Results: Without cytokine treatment, 20-ho ur-old PMNs showed marked apoptosis, no appreciable chemotaxis, and no ability to kill Candida albicans. In contrast, cytokine treatment sig nificantly reduced apoptosis and protected chemotaxis, C. albicans kil ling, and surface-receptor expression from both storage and irradiatio n, Although the majority of the benefit appeared to be due to G-CSF, c onsistent trends suggested better function of PMNs after combined trea tment with interferon-gamma and G-CSF. Conclusion: Judicious use of cy tokines may preserve PMN function. These findings have important impli cations for the transfusion of PMNs to cytopenic patients.