Recombinant granulocyte-macrophage colony-stimulating factor modulates in vitro function of the peripheral blood...

The effect of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) on the in vitro proliferation of peripheral blood lymphocytes (PBL) was evaluated in patients with lipoid nephrosis (LN). The cytokine increased the proliferation of LN PBL in response to phytohemagglutinin (PHA), measured by the [3H]thymidine uptake. The effects were abrogated by antibody against human GM-CSF. We then investigated the effect of GM-CSF on the release of interleukin-1 (IL-1) from peripheral blood monocytes (PBM) in LN patients and normals. In vitro IL-1 production by LN PBM treated with lipopolysaccharide (LPS) was enhanced by coculture with GM-CSF. Potentiation was approximately 2-fold. The immunological identity of the thymocyte comitogenic activity as IL-1 was confirmed by neutralization with a specific rabbit antihuman IL-1 antiserum. Taken together, these observations suggest that one mechanism by which GM-CSF acts to restore immune responses in LN patients may be enhancing the signals which enable activated monocytes/macrophages to secrete IL-1.