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

Immunol Lett. 2000 Jun 1;72(3):153-7. doi: 10.1016/s0165-2478(00)00178-4.


A novel pathway of autocrine macrophage activation based on a positive feedback loop involving interleukin (IL)-12, IL-18 and IFN-gamma has recently been suggested. However, the macrophage isolation technique employed to describe the above phenomenon does not allow obtaining a pure population of macrophages 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 oxide after stimulation with IL-12 and/or IL-18. Based on these observations we hypothesize that proposed autocrine feedback loop of macrophage activation is rather paracrine in nature and involves direct stimulation of residual lymphoid cells to secrete IFN-gamma that is then capable of activating macrophages.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cells, Cultured
  • Interferon-gamma / biosynthesis*
  • Interleukin-12 / immunology*
  • Interleukin-12 / pharmacology
  • Interleukin-18 / immunology*
  • Interleukin-18 / pharmacology
  • Macrophage Activation / drug effects
  • Macrophage Activation / immunology*
  • Macrophages, Peritoneal / drug effects
  • Macrophages, Peritoneal / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Nitric Oxide / biosynthesis
  • Recombinant Proteins / immunology
  • Recombinant Proteins / pharmacology


  • Interleukin-18
  • Recombinant Proteins
  • Interleukin-12
  • Nitric Oxide
  • Interferon-gamma