|Causes and Mechanisms of Linear Growth Retardation (International Dietary Energy Consultative Group - IDECG, 1993, 216 pages)|
|The effects of the inflammatory response on bone growth|
Interferons were named because they were first discovered to interfere with viral replication. (Isaacs & Lindenmann, 1957). However, as with many cytokines, it has since become clear that the actions of interferon gamma (IFNg) are more diverse than the early discoveries suggested. Although IFNg is produced primarily by T cells, natural killer cells and macrophages have also been suggested as sources (Trinchieri et al., 1984).
In culture, IFNg is a potent inhibitor of bone resorption. In bone explants, it inhibits osteoclast differentiation (Vignery, Niven & Shepard, 1990), and reduces the activity of existing cells in a manner similar to calcitonin (Klaushofer et al., 1989). The actions of IFNg are highly specific. It has been shown to inhibit resorption stimulated by IL-1 and TNF. The actions on resorption stimulated by PTH or the active metabolite of vitamin D are more variable different groups finding no effect (Gowen, Nedwin & Mundy, 1986) or inhibition (Fuji) et al., 1990; Nanes et al., 1990). The mechanism of action of IFNg is not clear, as it has been shown that it is not associated with changes in receptors for IL-1 (Shen et al., 1990). It is likely that it involves the inhibition of synthesis and release of the metalloproteinases necessary for matrix degradation (Shen et al., 1988). In addition, IFNg inhibits DNA synthesis in cell cultures, an effect which is enhanced by co-incubation with TNF (Napes, McKoy & Marx, 1989).
The action of interferon in vivo is in contrast with its clear ability to inhibit bone resorption in vitro. Although there are limited numbers of experiments to support this, Epstein showed a lack of effect of IFNg on most markers of cyclosporin-induced bone loss in rats (Jacobs et al., 1992). In addition, some parameters measured showed an increase in resorption. Vignery showed an increase in numbers of osteoclasts in mice following IFNg treatment (Vignery, Niven & Shepard, 1990), which is the opposite of the effect in vitro (Takahashi, Mundy & Roodman, 1986).