GROWTH OF LISTERIA-MONOCYTOGENES IN MURINE MACROPHAGES AND ITS MODULATION BY CYTOKINES - ACTIVATION OF BACTERICIDAL ACTIVITY BY INTERLEUKIN-4 AND INTERLEUKIN-6

Bone marrow derived macrophages were infected with a virulent strain of Listeria monocytogenes, and the ability of selected cytokines to modify the intracellular growth was assessed. Macrophage monolayers pretreated with either interferon-gamma or tumour necrosis factor were shown to exert a significant listericidal activity. Treatment of monolayers with granulocyte-macrophage colony stimulating factor led to no significant difference in the ability of Listeria to invade and multiply within these cells. Moreover, pulsing of macrophage monolayers with interleukin-6 (IL-6) led to a slight enhancement of Listeria growth in the macrophages, whereas interleukin-4 (IL-4) did not modify Listeria growth. In other sets of experiments, macrophage monolayers were treated with cytokines after phagocytosis of the bacteria. In these conditions, interferon-gamma endowed macrophages with only a modest ability to kill Listeria. Conversely, treatment of monolayers with IL-6 or IL-4 at the time of infection led to expression of high bactericidal activity. Collectively, these results suggest that macrophages may respond to different signals, which enhance their antimicrobial activity before or after infection. Furthermore, B-cell stimulatory factors (IL-4 and IL-6) are potent macrophage-activating molecules.