Regulation of mammary gland macrophage tumour necrosis factor-alpha production with interferon-gamma

Recombinant bovine interferon (rBoIFN)-gamma was found to modify the production of tumour necrosis factor (TNF-alpha) 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-gamma either three hours before or three hours following stimulation with LPS. The level of TNF-alpha 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-alpha when compared with non-treated cultures and those treated with only 1 U of interferon (IFN)-gamma. These results indicate that IFN-gamma is capable of down-regulating the production of TNF-alpha by a local macrophage population. The ability of IFN-gamma to modify the production of TNF-alpha 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-gamma may be directly responsible for down-regulation of acute phase inflammatory responses which may prevent pathological alterations to host tissues during endotoxaemia.