Effect of Endotoxin on Serum Granulocyte and Granulocyte-Macrophage Colony-Stimulating Factor Levels in Dogs

Abstract

The biologic effects of endotoxin are attributed to the release of several cytokines, including interleukin-l, interleukin-6, tumor necrosis factor, and the colony-stimulating factors. To investigate the mechanism of endotoxin-induced neutrophilia in dogs, several cell lines known to proliferate selectively in response to recombinant human colony-stimulating factors were examined to determine their responses to recombinant canine granulocyte colony-stimulating factor (rcG-CSF) or recombinant canine granulocyte-macrophage colony-stimulating factor (rcGMCSF). The murine cell line NFS-60 was found to respond well to rcG-CSF and the human cell line TALL-IOI to rcGM-CSF, and these responses were neutralized by antibodies to these recombinant proteins. These bioassays were then used to determine G-CSF and GM-CSF levels in dogs after intravenous endotoxin administration. G-CSF levels increased by 2 h, peaked at 4 h, and had not returned to normal by 24 h after endotoxin. In contrast, GM-CSF was not detectible before or after endotoxin administration.