Endotoxin is a toxic cell-wall component of Gramnegative bacteria consisting of lipopolysaccharide (LPS) and is present in large quantities in the intestine as a result of bacterial death and release during active growth. Small amounts of these LPSs are regularly absorbed but are rapidly detoxified by the liver which stands as a barrier to bacterial toxins which arise in the gut. For years, investigators have been intrigued by the possibility that failure to perform normally this function of detoxification might initiate or perpetuate liver injury, or result in systemic effects (1). This article reviews experimental and clinical evidence for a relationship between hepatic reticuloendothelial cells, endotoxin of gut origin, and liver injury.
The hypothesis to be examined is as follows: as is illustrated in Figure 1. (a) Portal vein endotoxemia of gut origin represents a normal physiologic state. (b) The hepatic sinusoidal cells, particularly fixed macrophages, are critical to normal endotoxin detoxification. (c) The initial damage in a number of injuries is to sinusoidal cells, which seriously impair the ability of the liver to handle the ordinarily innocuous amount of LPS coming from the gut. (d) This marked increase in sensitivity to LPS (which may be of a magnitude of 10-to 1,000-fold) leads to further hepatocyte damage and spillover of LPS into the systemic circulation which results in extrahepatic manifestations including hypergammaglobulinemia.
EVIDENCE FOR SYNERGISM
Several studies suggest a relationship between the intestinal tract and liver injury. In 1941, Leach showed that sulfonamides protected again carbon tetrachloride (CCL) liver injury (2). In 1954, a relationship was established between diet-induced liver injury and the presence of intestinal flora. Rats fed the necrogenic diet of Himsworth regularly died of liver necrosis in 35 days, whereas