INTERLEUKIN-4 INHIBITS MURINE OSTEOCLAST FORMATION INVITRO

Interleukin 4 (IL-4) is a product of activated T cells and mast cells with effects on immunologic and hematopoietic processes. We now report that IL-4 inhibits the formation of osteoclasts from murine bone marrow cells cocultured with stromal cells. Numerous (3,000-4,000 cells/2 cm2) tartrate-resistant acid-phosphatase-positive multinucleated cells with the capacity to generate cAMP in response to salmon calcitonin (ED50 = 10(-10) M) developed within 10-12 days of culture. IL-4 (ID50 = 10 U/ml) inhibited osteoclast generation in doses similar to those that induce proliferation of IL-4-responsive T cells. Additionally, the rat antimurine IL-4 monoclonal antibody 11B11 antagonizes the IL-4-inhibitory effect on osteoclast formation. These results suggest that IL-4 impedes agonist-induced in vitro bone resorption by inhibiting osteoclastogenesis.