Macrophages that kill glioma cells expressing the membrane form of macrophage colony stimulating factor are resistant to prostaglandin E2 and interleukin-10

Malignant rat T9 glioma cells retrovirally transduced with the membrane for m of macrophage colony stimulating factor (mM-CSF) were killed by bone marr ow derived macrophages in 24 h cytotoxicity assays. Prostaglandin E2 (PGE) and interleukin-10 (IL10) were tested for their ability to block this tumor icidal reaction. Only at very high nonphysiological concentrations of PGE ( 10(-5) and 10(-6) M) was this cytotoxicity inhibited. Use of high doses of theophylline, a phosphodiesterase inhibitor, also prevented macrophages fro m killing the mM-CSF transduced target cells. IL10 did not alter the killin g potential of the mM-CSF tumoricidal macrophages, even though IL10 reduced the production of nitric oxide by macrophages in response to tumor necrosi s factor and lipopolysaccharide. IL10 enhanced the growth of bone marrow ma crophages suggesting that IL10 has a complex role in the regulation of tumo ricidal macrophages. Thus, the mM-CSF may be an ideal agent to treat tumors that utilize either of these two immunosuppressive defense mechanisms that may block other forms of treatment. (C) 1999 Elsevier Science B.V. All rig hts reserved.