Protection of human polymorphonuclear leukocyte function from the deleterious effects of isolation, irradiation, and storage by interferon-gamma and granulocyte-colony-stimulating factor.

ABSTRACT

BACKGROUND: Fungal infections represent a difficult challenge to clinicians caring for neutropenic patients with hematologic malignancies, as antifungal therapy often has limited success in that setting. One promising yet problematic alternative approach is leukocyte transfusion. The isolation of polymorphonuclear leukocytes (PMNs) induces apoptosis and functional deterioration, and irradiation to prevent transfusion-associated graft-versus-host disease causes further functional deterioration. 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 culture (as a model for function after transfusion) and irradiation with 0, 5, or 30 Gy was studied. RESULTS: Without cytokine treatment, 20-hour-old PMNs showed marked apoptosis, no appreciable chemotaxis, and no ability to kill Candida albicans. In contrast, cytokine treatment significantly reduced apoptosis and protected chemotaxis, C. albicans killing, and surface-receptor expression from both storage and irradiation. Although the majority of the benefit appeared to be due to G-CSF, consistent trends suggested better function of PMNs after combined treatment with interferon-gamma and G-CSF. CONCLUSION: Judicious use of cytokines may preserve PMN function. These findings have important implications for the transfusion of PMNs to cytopenic patients.