INTERLEUKIN-4 MODULATES OSTEOCLAST DIFFERENTIATION AND INHIBITS THE FORMATION OF RESORPTION PITS IN MOUSE OSTEOCLAST CULTURES

Interleukin-4 (IL-4) is a well known lymphocyte growth factor, but it may also modulate the activity of other cell types. In the present study we show that IL-4 exerts a potent dose-dependent inhibitory effect on the resorptive activity of mouse bone cells, measured as the number of resorption pits (decreased down to 14% of control, p < 0.001) or the total resorbed area (down to 20% of control, p < 0.01). The results obtained in bone marrow and unfractionated bone cell cultures indicate that such an effect is mainly due to an inhibition of osteoclast precursors differentiation, rather than to a reduced activity of mature osteoclasts, and is not mediated by the IL-4-induced release of other soluble inhibitory factors. Likewise, although IL-4 may stimulate M-CSF expression, its inhibitory effect on osteoclast recruitment was not prevented by anti-M-CSF antibodies, suggesting that it was not mediated by M-CSF. These results point out IL-4 as an potentially important regulatory factor of osteoclast differentiation. © 1993 Acdamic Press. Inc.