AUGMENTATION OF ALVEOLAR MACROPHAGE PHAGOCYTIC-ACTIVITY BY GRANULOCYTE-COLONY-STIMULATING FACTOR AND INTERLEUKIN-1 - INFLUENCE OF SPLENECTOMY

The use of cytokines and other naturally occurring substances as biopharmaceuticals for modulating the host response to trauma and infection offers new therapeutic possibilities. Cytokine pretreatment protects animals in a variety of experimental models, including splenectomized mice following pneumococcal aerosol challenge. Since splenectomy appears to affect alveolar macrophage function, we postulated that pretreatment with interleukin 1 (IL-1) and granulocyte colony stimulating factor (G-CSF) improved survival in mice following aerosol challenge of live pneumococci by activating alveolar macrophages. Alveolar macrophage bactericidal and phagocytic function was slightly, but consistently, depressed following splenectomy. Interleukin-1 and G-CSF pretreatment had pronounced effects on macrophage phagocytic and bactericidal activity, and these effects were quite different depending upon whether the mice were eusplenic or asplenic. Splenectomy augmented the effects of IL-1 on alveolar macrophage bactericidal function compared with eusplenic mice (p < 0.001), while more pronounced effects on macrophage function following G-CSF treatment were seen in mice with intact spleens (p < 0.001). The use of cytokines and other substances to modify the host response to infection has great potential. Individuals with deficits such as splenectomy will have a different net response to therapy. It is important that we be able to predict these responses accurately in most patients in order to use these substances more effectively.