Monokine depression of bile flow in the isolated perfused rat liver

Multiple system organ failure (MSOF) is a progressive dysfunction of vital organs that may develop in clinical settings such as sepsis or multiple trauma. One component of this syndrome is cholestasis and impaired liver function. The mechanism(s) for this liver failure (and the failure of other organs) remains obscure. Macrophages and Kupffer cells have been shown to secrete cytokines such as interleukin-1 and tumor necrosis factor. These cytokines mediate many aspects of the acute phase response, and they also can produce cellular injury. The purpose of this study was to evaluate the effects of a semipurified murine monokine preparation having interleukin-1 activity on bile flow in the rat isolated perfused liver (IPL). The monokine preparation produced a significant reduction of bile flow in the IPL system. The effect could not be explained by a venoocclusive phenomenon or residual endotoxin in the monokine preparation. We conclude that a semipurified monokine preparation having interleukin-1 but not tumor necrosis activity produced a significant depression of bile flow in the IPL, and we suggest that macrophage secretory product(s) may be responsible for the cholestasis in MSOF.