INHIBITORY EFFECT OF INTERLEUKIN-4 ON OSTEOCLAST-LIKE CELL-FORMATION IN MOUSE BONE-MARROW CULTURE

Recently, interleukin 4 (IL-4) was reported to inhibit bone resorption in mouse long bone culture. To test the effect of IL-4 on the formation of osteoclast-like cells. we used a mouse bone marrow culture system that formed mononuclear and multinucleated cells with osteoclast characteristics. Recombinant mouse IL-4 dose-dependently inhibited the formation of tartrate-resistant acid phosphatase-positive multi-nucleated cells [TRAP(+)MNC) induced by 1,25(OH)2D3, PTH(1-34) or interleukin-1alpha (IL-1alpha). The minimum effective inhibitory concentration was 0.01 ng/ml, and 1 ng/ml IL-4 completely inhibited TRAP(+)MNC formation. IL-4 also dose-dependently inhibited the formation of tartrate-resistant acid phosphatase-positive mononuclear cells. Treatment of cultures with IL-4 for the first or last 48 h of an 8-day culture period inhibited TRAP(+)MNC formation to the same extent, whereas IFN-gamma and calcitonin suppressed TRAP(+)MNC formation mainly at the early and the late phase. respectively. IL-4, as a macrophage fusion factor, at higher concentrations (0.1 is similar to 10 ng/ml), increased formation of tartrate-resistant acid phosphatase-negative multinucleated cells [TRAP(-)MNC] with giant macrophage characteristics. The half-maximal concentrations inhibiting TRAP(+)MNC formation and stimulating TRAP(-)MNC formation were 0.05 ng/ml and 2 ng/ml, respectively. These results demonstrate that IL-4 inhibits bone resorption by inhibiting the recruitment of osteoclast precursor and formation of multinucleated osteoclast-like cells, and by stimulating the formation of macrophage polykarions.