Regulation of mammary gland macrophage tumour necrosis factor-α production with interferon-γ

Recombinant bovine interferon (rBOIFN)-γ was found to modify the production of tumour necrosis factor ( TNF-α) production by lipopolysaccharide (LPS) stimulated mammary gland macrophages. Alveolar macrophages isolated from bovine mammary glands were incubated with 0, 1, 10, 100 or 1000 U of rBOIFN-γ either three hours before or three hours following stimulation with LPs. The level of TNF-α production was not affected when macrophages were treated with rBoiFN before LPs stimulation. In contrast, macrophages treated with 10,100 or 1000 U of rBOIFN after stimulation with LPs produced significantly lower concentrations Of TNF-α when compared with non-treated cultures and those treated with only 1 U of interferon (IFN)-γ. These results indicate that IFN-γ is capable of down-regulating the production of TNF-α by a local macrophage population. The ability of IFN-γ to modify the production of TNF-α is dependent on the timing of administration relative to LPs exposure. The significance of these findings is that under some circumstances, low dose administration of IFN-γ may be directly responsible for down-regulation of acute phase inflammatory responses which may prevent pathological alterations to host tissues during endotoxaemia.