INDUCTION BY INTERFERONS OF HUMAN EOSINOPHIL APOPTOSIS AND REGULATIONBY INTERLEUKIN-3, GRANULOCYTE MACROPHAGE-COLONY STIMULATING FACTOR AND INTERLEUKIN-5/

The effects of recombinant human interferon alpha (rhIFN-alpha) and in terferon gamma (rhIFN-gamma) were examined on the apoptosis of human c ord blood derived eosinophils, obtained after 4 weeks of culture with recombinant human interleukin-3 (rhIL-3), granulocyte-macrophage-colon y stimulating factor (rhGM-CSF) and interleukin-5 (rhIL-5). Eosinophil viability decreased remarkably after 1 week culture with rhIFN-alpha and rhIFN-gamma. Recombinant rhIFN-alpha also decreased the viability of co-existing monocytes/macrophages, whereas in contrast, rhIFN-gamma increased the percentage of viable monocytes/macrophages. There was n o synergistic or additional effect of rhIFN-alpha and rhIFN-gamma on e osinophil viability. Apoptotic eosinophils, detected by their morpholo gical characteristics, or by DNA nick end labeling in situ, increased remarkably after incubation with rhIFN-alpha and increased to a lesser extent with rhIFN-gamma. The numbers of eosinophil-phagocytosing macr ophages increased after culture with rhIFN-alpha and also with rhIFN-g amma. In contrast, eosinophilopoietic cytokines such as rhIL-3, rhIL-5 and specially rhGM-CSF, significantly increased eosinophil viability, and partially rescued the effects of rhIFNs, They also decreased apop totic eosinophil numbers and eosinophil-phagocytosing macrophage numbe rs. These results indicate that eosinophil viability, at least in vitr o, can be differentially regulated by cytokines produced during the im mune response.