Although more than two dozen factors have been implicated in control of the macrophage response to inflammation, five of these are believed to play dominant roles. They are shown in Figure 1 and consist of (1) tumor necrosis factor (TNF), (2) interleukin-1 (IL-1), (3) granulocyte-monocyte colony-stimulating factor (GM-CSF), (4) granulocyte colony-stimulating factor (G-CSF), and (5) monocyte colony-stimulating factor (M-CSF). These factors are formed by activated macro phage cells in the inflamed tissues and in smaller quantities by other inflamed tissue cells.
Fig1. Control of bone marrow production of granulocytes and monocyte-macrophages in response to multiple growth factors released from activated macrophages in an inflamed tissue. G-CSF, granulocyte colony-stimulating factor; GM-CSF, granulocyte monocyte colony-stimulating factor; IL-1, interleukin-1; M-CSF, monocyte colony-stimulating factor; TNF, tumor necrosis factor.
The cause of increased production of granulocytes and monocytes by the bone marrow is mainly the three colony-stimulating factors, one of which, GM-CSF, stimulates both granulocyte and monocyte production; the other two, G-CSF and M-CSF, stimulate granulocyte and monocyte production, respectively. This combination of TNF, IL-1, and colony-stimulating factors provides a powerful feedback mechanism that begins with tissue inflammation and proceeds to formation of large numbers of defensive WBCs that help remove the cause of the inflammation.
