Interferon and tumor necrosis factor production during endotoxemia in sheep

In humans endotoxemia has often been associated with the development of adult respiratory distress syndrome (ARDS). Sheep have an abundant population of pulmonary intravascular macrophages, therefore they are a popular animal model for ARDS. In this study we characterized the temporal sequence and duration of the release of two cytokines: tumor necrosis factor (TNF) and interferon (IFN) and evaluated the effect of lipopolysaccharide (LPS) dose. Rectal temperature and white blood cell (WBC) count were also measured. Twenty four adult sheep were given E. coli endotoxin at a dose of 0 (saline solution) 0.05, 0.1 and 1.0 microg/kg of body weight by intravenous (i.v.) bolus. In all groups, TNF-alpha was produced earlier (3-4.5 h) after injection than IFN (4-5 h). No correlation between increased rectal temperature, the magnitude of leukopenia and time course of both cytokines production was observed. No straight relationship between LPS dose and the titer of cytokines was seen, but lower doses of LPS-induced delayed cytokine response in comparison to the dose 1 microg/kg of LPS. As IFN, present in the circulation of sheep, was mainly alpha/beta type, the role of this class of IFN in endotoxemia is discussed.