Direct stimulation of macrophages by IL-12 and IL-18 - a bridge too far?

A novel pathway of autocrine macrophage activation based on a positive feed back loop involving interleukin (IL)-12, IL-18 and IFN-gamma has recently b een suggested. However, the macrophage isolation technique employed to desc ribe the above phenomenon does not allow obtaining a pure population of mac rophages casting some doubt to its existence. In the present study, we show that even minor contamination with lymphoid cells of a pure population of macrophage-like cells (Raw 264.7) results in a marked production of nitric oxide after stimulation with both IL-12 and IL-18. Neither macrophage-like cells nor lymphoid cells were capable of secreting high amounts of nitric o xide after stimulation with IL-12 and/or IL-18, Based on these observations we hypothesize that proposed autocrine feedback loop of macrophage activat ion is rather paracrine in nature and involves direct stimulation of residu al lymphoid cells to secrete IFN-gamma that is then capable of activating m acrophages. (C) 2000 Elsevier Science B.V. All rights reserved.