Synergistic action of recombinant-derived murine interleukin-1 on the augmentation of colony stimulating activity on murine granulocyte-macrophage hematopoietic stem cells in vitro.

Abstract

This communication reports studies that were designed to investigate the role of recombinant-derived murine interleukin-1 on granulocyte macrophage (CFU-GM) progenitor stem cells in vitro. Interleukin-1 (IL-1, 5-25 units/ml culture) in a dose-dependent fashion, stimulated CFU-GM with a maximum effect at 25 units (147.3 +/- 6.4 colonies/10(5) nonadherent-derived marrow cells). At a higher concentration (50 units/ml) this stimulation was significantly reduced. IL-1, in combination with various types of conditioned media: pokeweed mitogen stimulated spleen cell, mouse lung and WEHI-3 cell, as a source of colony-stimulating activity (CSA), produced more CFU-GM when compared to controls (conditioned media alone). Furthermore, when assayed for their esterase activity, IL-1 increased both types of nonspecific and specific esterase content in CFU-GM colonies. Also, the actual ratio between neutrophilic and monocyte/macrophage colonies was reduced when compared to cultures stimulated in the presence of CSA, indicating that IL-1 increased myeloid differentiation. In the presence of indomethacin, an effective inhibitor of prostaglandin synthesis (1 microgram/ml), greater numbers of CFU-GM were present with IL-1 and/or CSA than without indomethacin. Cultures with anti-CSA demonstrated a reduced number of CFU-GM when plated in the presence of CSA but not with IL-1, demonstrating the specificity of IL-1 to stimulate CFU-GM in the presence of anti-CSA antibody. These results indicate a role for IL-1 in modulating granulopoiesis in vitro.