REGULATION OF MAMMARY-GLAND MACROPHAGE TUMOR-NECROSIS-FACTOR-ALPHA PRODUCTION WITH INTERFERON-GAMMA

Recombinant bovine interferon (rBOIFN)-gamma was found to modify the p roduction of tumour necrosis factor (TNF-alpha) production by lipopoly saccharide (LPS) stimulated mammary gland macrophages. Alveolar macrop hages isolated from bovine mammary glands were incubated with 0, 1, 10 , 100 or 1000 U of rBOIFN-gamma either three hours before or three hou rs following stimulation with LPS. The level of TNF-alpha production w as not affected when macrophages were treated with rBOIFN before LPS s timulation. In contrast, macrophages treated with 10, 100 or 1000 U of rBOIFN after stimulation with LPS produced significantly lower concen trations of TNF-alpha when compared with non-treated cultures and thos e treated with only 1 U of interferon (IFN)-gamma. These results indic ate that IFN-gamma is capable of down-regulating the production of TNF -alpha by a local macrophage population. The ability of IFN-gamma to m odify the production of TNF-alpha is dependent on the timing of admini stration 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 inflam matory responses which may prevent pathological alterations to host ti ssues during endotoxaemia.