Although altered cytokine homeostasis has been implicated in the pathogenesis of alcoholic liver disease, the relationship between cytokines and metabolic consequences of alcoholic liver disease is unknown. We, therefore, sought to correlate circulating concentrations of tumor necrosis factor-alpha, interleukin-1 and interleukin-6 to clinical and biochemical parameters of liver disease in chronic alcoholic patients. We used an enzyme-linked immunosorbent assay to measure plasma tumor necrosis factor and interleukin-1 and a bioassay to measure serum interleukin-6 in three groups of alcoholic men as follows: (a) actively drinking alcoholic men without evidence of chronic liver disease, (b) nondrinking alcoholic men with stable cirrhosis and (c) patients with acute alcoholic hepatitis. Mean cytokine concentrations were elevated in cirrhotic patients and alcoholic hepatitis patients compared with controls and alcoholic patients without liver disease. Tumor necrosis factor-alpha and interleukin-1 alpha concentrations remained elevated for up to 6 mo after diagnosis of alcoholic hepatitis, whereas interleukin-6 normalized in parallel with clinical recovery. Concentrations of all three cytokines were correlated with biochemical parameters of liver injury and hepatic protein synthesis plus serum immunoglobulin concentrations. We could not demonstrate a relationship between cytokine concentrations and peripheral endotoxemia. Percentages of peripheral blood monocytes that reacted with monoclonal antibodies to CD25 (interleukin-2 receptor) and human lymphocyte antigen-DR were similar for alcoholic patients and controls. These data suggest that tumor necrosis factor-alpha and interleukin-1 alpha are related to some of the metabolic consequences of both acute and chronic alcohol-induced liver disease, whereas interleukin-6 is related to abnormalities seen in acute liver injury.

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The hypothesis that dietary fiber lowers serum cholesterol was tested in 10 healthy men, 19 to 54 years old, who ate a mixed diet similar to the diets of many American adult males, that contained 16% of calories as protein (70% from animal), 40% as fat (P/S = 0.3), 44% as carbohydrate (9% of calories as sucrose) and 3 g of crude fiber. The energy intake ranged from 2700 to 3500 kcal adjusted to their height and weight. Weight and fitness were held constant. After 30 days of equilibration on the basal diet, they ate 26 g of either soft white wheat bran, corn bran (CB), soybean hulls (SH), textured vegetable protein, or hard red spring wheat bran (HRS) for periods of 28 to 30 days each in no particular sequence. Each fiber was fed to four to six subjects. The dietary fiber contents of soft white wheat bran, CB, SH, and HRS were: 44, 92, 87, and 51%, respectively. Mean daily fecal weight increased (P less than or equal to 0.01) from 72.4 to 144, 68 to 128, and 81 to 151 g when CB, SH, and HRS were fed respectively. No effects were noted with soft white wheat bran or textured vegetable protein. Total plasma cholesterol decreased 12% with HRS (P less than or equal to 0.05) and 14.0% with SH (P less than or equal to 0.05). Low density lipoprotein cholesterol decreased 21% with HRS (P less than or equal to 0.05). High density lipoprotein cholesterol did not change with any of the dietary fiber sources nor did the ratio of high density lipoprotein cholesterol to total cholesterol. Some triglyceride lowering effect was seen with all sources of dietary fiber (P less than or equal to 0.01). There was a significant direct correlation between the area under the oral glucose tolerance curves and the levels of total cholesterol (r = 0.57, P less than or equal to 0.0001) and low density lipoprotein cholesterol (r = 0.49, P less than or equal to 0.0007), and between fasting plasma glucose and triglycerides (r = 0.32, P less than or equal to 0.03). Results were replicated when subjects were fed the same fiber source on two occasions at 2 to 4 month intervals.

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The concentration of porphyrin in bile is higher in patients with variegate porphyria than in controls, and the difference is greater than that for fecal porphyrin. Bile porphyrin measurements may be helpful in the evaluation of asymptomatic patients suspected of having variegate porphyria.