Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) Enhances Pulmonary Defenses Against Pneumococcal Infections after Splenectomy

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Abstract
Splenectomized individuals are at risk for pneumococcal sepsis. Alveolar macrophage bactericidal function is depressed after splenectomy. Granulocyte-macrophage colony-stimulating factor (GM-CSF) has pronounced effects on the number and function of macrophages. We hypothesized that GM-CSF treatment could improve alveolar macrophage bactericidal activity against pneumococci, and improve survival with pneumococcal infection. Two weeks after splenectomy or sham operation, mice were treated with GM-CSF or saline twice daily for varying times. Alveolar macrophages were obtained by bronchopulmonary lavage, and bactericidal activity was measured. Survival was assessed after pneumococcal aerosol challenge. Alveolar macrophage bactericidal activity was improved with GM-CSF treatment in both eusplenic and asplenic mice (p < 0.001). GM-CSF treatment improved survival in both groups (p < 0.001). GM-CSF can augment alveolar macrophage function and provide protection against pneumococcal infections. It may be a useful adjuvant therapy for normal and splenectomized individuals.