Effects of excess granulocyte-macrophage colony stimulating factor (GM-CSF) in mice infected with a GM-CSF retrovirus.

To study the effects of dysregulated granulocyte-macrophage colony stimulating factor (GM-CSF) production, a retroviral vector (MPZen) containing a GM-CSF cDNA has been used to infect murine bone marrow cells prior to their transplantation into lethally-irradiated recipients. Animals transplanted with 1 x 10(6) bone marrow cells 14 to 21 days after transplantation displayed shortness of breath, trembling to the touch, and dragging of the hind limbs. These animals were shown to have increased peripheral blood neutrophil counts (x 200), decreased marrow cellularity (but with increased neutrophil and macrophage frequency) and increased spleen cellularity (with up to a 40-fold increase in neutrophil, macrophage and eosinophil frequency). Examination of sections of tissues from infected mice showed massive infiltration of neutrophils and macrophages in muscle, lungs, liver, and variable infiltration of these cells in lymphoid tissues and the eye. Haemopoietic tissues produced high levels of GM-CSF (10(5) Units/10(6) cells) and the serum contained up to 5.5 x 10(5) Units of GM-CSF per ml.