The effects of interleukin (IL)-4 and IL-10 on macrophage growth-stimulating activities of oxidized low density lipoprotein (LDL), acetylated LDL and macrophage colony-stimulating factor: the activity of oxidized LDL is refractory to the inhibitory cytokines.

We have previously reported that ligands of scavenger receptor such as acetylated low density lipoprotein (acetyl-LDL) and oxidized LDL induced growth of peripheral macrophages in vitro. This suggests the possibility that in addition to foam cell formation, modified or oxidized LDLs induce macrophage proliferation in atherosclerotic lesions. To learn further the physiological regulation of macrophage growth, we comparatively examined the effect of interleukin (IL)-4 and IL-10 which have been reported to be suppressive to various macrophage functions on macrophage growth-stimulating activities of the acetyl-LDL, oxidized LDL and macrophage colony-stimulating factor (M-CSF). An in vitro study showed that the activity of M-CSF-containing L-cell-conditioned medium was the most sensitive to the suppressive effects of these cytokines. The growth-inducing activity of acetyl-LDL was significantly inhibited by both IL-4 and IL-10. On the other hand, the activity of oxidized LDL was not attenuated by IL-4 or IL-10. These data indicate that macrophage growth-stimulating activity of oxidized LDL, in contrast to that of M-CSF or acetyl-LDL, is refractory to these suppressive cytokines. Oxidized LDL may act as a potent macrophage growth-stimulating factor in atherosclerotic or other inflammatory sites, even when these cytokines are produced by inflammatory and immunological reactions in situ.