Effects of interferon and other cytokines on collagen synthesis in fetal rat bone cultures

Control of trabecular bone volume is mediated by local events. Recently, it has been shown that the cytokines interleukin-1 (IL-1), tumor necrosis factor a (TNFα), and TNFβ [also called lymphotoxin (LT)] produced by immune cells all stimulate osteoclast activity, whereas the lymphokine interferon-γ (IFNγ) inhibits osteoclast activity stimulated by these agents. We report here the effects of each of these cytokines on bone collagen content measured as incorporation of proline into collagen and noncollagen protein in 20-day-old fetal rat calvariae. We found that IL-1, LT, and TNF decreased bone collagen synthesis and, to a lesser degree, noncollagen protein synthesis when the bones were exposed continuously to these agents. In addition, these cytokines stimulated DNA synthesis in the calvariae. In contrast to its action on bone resorption, where it opposed the resorptive effects of IL-1, TNF, and LT, IFNγ inhibited bone collagen synthesis and had an additive effect with TNF and LT when bones were exposed to both. However, unlike the other cytokines, IFNγ also decreased DNA synthesis in the calvariae. These data indicate that cytokines released by immune cells in the bone marrow microenvironment may work in concert to affect osteoblast activity in vitro.