CYTOKINE PRODUCTION BY CALVARIAE OF OSTEOPETROTIC MICE

In the osteopetrotic op/op mouse, the absence of macrophage colony-sti mulating factor (M-CSF) prevents the growth of macrophages and osteocl asts and, consequently, bone resorption. In the present study, we inve stigated whether this deficiency in M-CSF production alters the produc tion of cytokines in op/op bones. Calvariae of phenotypically normal ( +/?) and op/op mice were stimulated in vitro with lipopolysaccharide o r Pasteurella multocida toxin to produce cytokines. Interleukin-3 (IL- 3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) synth esis was the same both in calvaria from osteopetrotic and phenotypical ly normal animals. However, the production of granulocyte colony-stimu lating factor (G-CSF), interleukin-6 (IL-6), and tumor necrosis factor -alpha (TNF alpha) was lower in calvaria from op/op animals than was t he case in +/? calvaria. Thus, the lack of biologically active M-CSF c auses defects which are not compensated by cells independent of M-CSF.