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Protection of human polymorphonuclear leukocyte function from the deleterious effects of isolation, irradiation, and
J H Rex1, S C Bhalla, D M Cohen
1Department of Internal Medicine, University of Texas-Houston Medical School, USA.
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.
Insights
Cytokine treatment, including granulocyte-colony-stimulating factor (G-CSF), preserves polymorphonuclear leukocyte (PMN) function after storage and irradiation. This enhances PMN transfusion efficacy for neutropenic patients with hematologic malignancies.
Area of Science:
- Hematology
- Immunology
- Cell Biology
Background:
- Fungal infections pose significant challenges for neutropenic patients with hematologic malignancies.
- Antifungal therapies have limited success, making leukocyte transfusions a problematic alternative.
- Polymorphonuclear leukocyte (PMN) isolation and irradiation impair function and induce apoptosis.
Purpose of the Study:
- To evaluate the protective effects of interferon-gamma and G-CSF on PMNs.
- To assess PMN function after storage and irradiation with cytokine treatment.
- To determine the optimal cytokine combination for preserving PMN function.
Main Methods:
- PMNs were stored for 0 or 20 hours and irradiated with 0, 5, or 30 Gy.
- Interferon-gamma and G-CSF were used alone and in combination.
- Apoptosis, chemotaxis, Candida albicans killing, and receptor expression were measured.
Main Results:
- Untreated PMNs showed apoptosis, reduced chemotaxis, and impaired C. albicans killing after 20-hour storage.
- Cytokine treatment significantly reduced apoptosis and preserved PMN function.
- G-CSF provided the majority of the protective effect, with combined therapy showing a trend towards better function.
Conclusions:
- Cytokine administration can preserve PMN function following storage and irradiation.
- These findings support the judicious use of cytokines to improve PMN transfusion outcomes.
- Optimized PMN transfusions may benefit cytopenic patients, particularly those with hematologic malignancies.