Interleukin 4 induces cultured monocytes/macrophages to form giant multinucleated cells

Giant multinucleated cells (GMCs) are associated with granulomatous lesions that form in response to various infectious and noninfectious agents. The present study shows that mouse IL-4 induces the in vitro formation of GMCs by factor-dependent bone marrow and alveolar monocytes via cell fusion. GMCs appear 2 d after incubation of cell cultures with 20 U/ml or more of IL-4. Anti-IL-4 mAbs block the appearance of GMCs in these cultures, indicating that IL-4 acts directly on monocytes to promote fusion and does not secondarily induce the production of other soluble fusion factors. In soft agar cultures, IL-4 also causes the aggregation of macrophages and diminishes their migration. The role of IL-4 in a granulomatous inflammatory response is discussed.