The mechanism of liver injury in endotoxemia is unclear. Previous studies have shown that splenectomy protects the liver from endotoxin-induced injury. The purpose of this study was to determine the relationship of TNFalpha and IFNgamma release and endotoxin-induced liver injury in splenectomized and nonsplenectomized rats. Splenectomized and nonsplenectomized (Sham) rats with chronic catheters in the aorta and inferior vena cava (IVC) were parenterally infused with 10 to 5000 microg/kg endotoxin. TNFalpha, IFNgamma, and alanine aminotransferase (ALT), a marker of hepatocellular damage, were measured in aortic blood. Compared to sham controls, splenectomized animals demonstrated significantly reduced endotoxin-induced ALT concentrations at endotoxin doses >10 microg/kg. Peak endotoxin-induced TNFalpha concentrations were not significantly different between the splenectomized and sham groups. In contrast, peak endotoxin-induced IFNgamma concentrations were significantly decreased in the splenectomized group. These data suggest a relationship between endotoxin-induced IFNgamma and liver injury. We speculate that the spleen contributes to the endotoxin-induced liver injury by modulating release of IFNgamma.
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