Colony-stimulating factors: Beyond the effects on hematopoiesis

Abstract

The effects of sargramostim and filgrastim on hematopoietic cells are described. Filgrastim is a lineage-specific colony-stimulating factor (CSF), mainly affecting neutrophils. In addition to enhancing neutrophil recovery, filgrastim may also enhance neutrophil functional activity. Filgrastim does not have any meaningful effect on monocytes or macrophages; however, recent data indicate that filgrastim has a stimulatory effect on Th2 lymphocyte-inducing dendritic cells. These dendritic cells facilitate humoral immune responses, but they also produce inhibitory cytokines that diminish cell-mediated immunity. Sargramostim is a multilineage CSF, affecting neutrophils, monocytes, macrophages, and dendritic cells. Sargramostim has a greater impact on Th1 lymphocyte-inducing dendritic cells, which facilitate cell-mediated immune responses, including antitumor activity. The broader activity of sargramostim on both types of antigen-presenting cells (macrophages and dendritic cells) may account for the reports of benefit beyond enhanced neutrophil recovery that have been seen in clinical trials of patients with leukemia and patients undergoing stem-cell transplantation. Given the disparate activity of these two CSFs on the immune system and the types of immune responses generated, it is prudent for clinicians to consider these effects when choosing an agent for enhancing neutrophil recovery in various clinical settings.