Pathophysiology Of Liver Disease Research Articles

Circulating interleukin-1 and tumor necrosis factor antagonists in liver disease

The proinflammatory cytokines interleukin-1 and tumor necrosis factor-alpha are thought to play important roles in the pathophysiology of liver disease. Specific antagonists of these cytokines have been found in recent years. Interleukin-1 receptor antagonist is a specific interleukin-1 antagonist. The soluble receptor derived from the cell-surface p55 tumor necrosis factor receptor p55 is a naturally occurring substance that inhibits the biological effects of tumor necrosis factor. We used specific radioimmunoassays to detect circulating interleukin-1 receptor antagonist and tumor necrosis factor soluble receptor p55 levels in 14 patients with acute viral hepatitis and in 160 patients with various chronic liver diseases. Levels of interleukin-1 receptor antagonist and, especially, tumor necrosis factor soluble receptor were markedly increased in most patients with chronic liver disease regardless of pathogenesis and in viral hepatitis. Patients with chronic liver disease and cirrhosis showed significantly higher levels of both cytokine antagonists than did noncirrhotic patients. Correlations between interleukin-1 receptor antagonist and tumor necrosis factor soluble receptor were more significant than those of either antagonist with C-reactive protein or blood sedimentation rate. Interleukin-1 receptor antagonist and tumor necrosis factor soluble receptor levels were also positively correlated with bilirubin and AST levels. We conclude that circulating levels of interleukin-1 receptor antagonist and tumor necrosis factor soluble receptor may reflect ongoing disease activity and probably modulate some effects of endogenous interleukin-1 and tumor necrosis factor.

Circulating interleukin-1 and tumor necrosis factor antagonists in liver disease

The proinflammatory cytokines interleukin-1 and tumor necrosis factor-α are thought to play important roles in the pathophysiology of liver disease. Specific antagonists of these cytokines have been found in recent years. Interleukin-1 receptor antagonist is a specific interleukin-1 antagonist. The soluble receptor derived from the cell-surface p55 tumor necrosis factor receptor p55 is a naturally occurring substance that inhibits the biological effects of tumor necrosis factor. We used specific radioimmunoassays to detect circulating interleukin-1 receptor antagonist and tumor necrosis factor soluble receptor p55 levels in 14 patients with acute viral hepatitis and in 160 patients with various chronic liver diseases. Levels of interleukin-1 receptor antagonist and, especially, tumor necrosis factor soluble receptor were markedly increased in most patients with chronic liver disease regardless of pathogenesis and in viral hepatitis. Patients with chronic liver disease and cirrhosis showed significantly higher levels of both cytokine antagonists than did noncirrhotic patients. Correlations between interleukin-1 receptor antagonist and tumor necrosis factor soluble receptor were more significant than those of either antagonist with C-reactive protein or blood sedimentation rate. Interleukin-1 receptor antagonist and tumor necrosis factor soluble receptor levels were also positively correlated with bilirubin and AST levels. We conclude that circulating levels of interleukin-1 receptor antagonist and tumor necrosis factor soluble receptor may reflect ongoing disease activity and probably modulate some effects of endogenous interleukin-1 and tumor necrosis factor. (HEPATOLOGY 1993;18:1132-1138).

Autoantibodies against nuclear envelope proteins in liver disease

The contents of the cell nucleus are separated from the cytoplasm by the nuclear envelope. The nuclear envelope is composed of the nuclear membranes, the nuclear pore complexes and the nuclear lamina. In recent years, cell biologists have characterized some of the protein components of these structures and have begun to understand their functions in nucleocyto-plasmic transport, chromatin organization and nuclear dynamics of cell division. Autoantibodies against major protein components of the nuclear envelope are found in patients with many liver disease. These findings suggest that certain antibody specificities may be characteristic of clinical syndromes and may be useful in classifying patients with these diseases. The demonstration of nuclear envelope proteins as antigens in liver diseases also raises the question of whether these proteins are involved in the pathophysiology of certain liver disorders. For these reasons, the nuclear envelope has become a cell structure of interest not only to basic cell biologists, but also to hepatologists. In this article, we review the cell biology of the nuclear envelope and its major protein components, the studies characterizing autoantibodies against nuclear envelope proteins and the potential roles of nuclear envelope proteins in the pathophysiology of liver diseases.

Clinical and experimental Studies on the pathophysiology of liver diseases and intravscular coagulation

The clinical and experimental findings related to the mechanism of hepatic cell necrosis in associated with intravascular coagulation were studied.The results and conclusion of our work are summarized as follows.1) Endotoxemia as detected by the Limulus Test, was often found in the patients with fulminant hepatitis and the close correlation found between the development of endotoxemia and the occurence of both renal impairment and intravascular coagulation.2) Experimental endotoxin D. I. C. and liver cell necrosis.E. coli endotoxin was injected into the rabbit portal vein and 24 hours later a ten-fold dose of endotoxin was injected in an ear vein.Extensive liver necrosis was found which was complicated by fibrin microthrombi in the Sinusoid or necrotic area.Similar changes were found in the kidneys and intestinal tract.In fluminant hepatitis complicated by D. I. C., the pathogenesis and haemorrhagic diathesis ressemble that was found in our experimental study.