INTERLEUKIN-4 INDUCES FOREIGN-BODY GIANT-CELLS FROM HUMAN MONOCYTES MACROPHAGES - DIFFERENTIAL LYMPHOKINE REGULATION OF MACROPHAGE FUSION LEADS TO MORPHOLOGICAL VARIANTS OF MULTINUCLEATED GIANT-CELLS

Interleukin-4 induced the formation of foreign body-type giant multinu cleated cells from human monocyte-derived macrophages, an effect that was optimized with either granulocyte-macrophage colony-stimulating fa ctor or interleukin-3, dependent on the concentration of interleukin-4 , and specifically prevented by anti-interleukin-4. Very large foreign body giant cells and, predominantly, giant cell syncytia with randoml y arranged nuclei and extensive cytoplasmic spreading (285 +/- 121 nuc lei and 1.151 +/- 0.303 mm(2) per syncytium) were consistently obtaine d. Under otherwise identical culture conditions, relatively much small er langhans-type giant cells with circularly arranged nuclei were indu ced with a previously described combination of interferon-gamma plus g ranulocyte-macrophage colony-stimulating factor or interleukin-3 (16 /- 6 nuclei and 0.033 +/- 0.013 mm(2) per giant cell); their formation was prevented by anti-interferon-gamma but not by anti-interleukin-4. Similar rates of macrophage fusion were obtained in both culture syst ems (72 +/- 5% and 74 +/- 6%, respectively), but these two morphologic al or form from one another within the 10-day culture period. These fi ndings demonstrate that interleukin-4 is a potent human macrophage fus ion factor and that differential regulation of macrophage fusion by in terleukin-4 and interferon-gamma may lead to morphological variants of multinucleated giant cells.