concanavalin-a and Liver-Cirrhosis--Alcoholic

The capacity of the liver to synthesize insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) may be compromised by alcohol. The characteristics of IGFBP-3 variants obtained from healthy individuals and patients with alcoholic cirrhosis (ALC) were compared. Concanavalin A (Con A) affinity electrophoresis and ligand blotting demonstrated that there was a gradual change in carbohydrate properties of putative IGFBP-3 with progression of ALC from stages A to C. As many as 12 ionic species of IGFBP-3 could be distinguished, corresponding probably to variously glycosylated and/or phosphorylated isoforms of the core protein. Three of them reacted significantly with the immobilized Con A, the pattern being altered in patients with ALC. Patients with ALC in stage B exhibited the presence of clearly differentiated IGFBP-3 variants less and more Con A reactive, suggesting this stage to be a turning point with the most intensive changes in the IGF - IGFBP system. Because the glycosylation pattern is tissue specific, pathological post-translational modifications found for one glycoprotein (IGFBP-3) are probably shared by others of the same tissue origin. This may affect their susceptibility to proteolysis and subsequently their function.

Topics: Adult; Concanavalin A; Humans; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor II; Ligands; Liver Cirrhosis, Alcoholic; Protein Isoforms

The role of T-cell activation in alcoholic liver disease was investigated in rats fed alcohol and subsequently exposed to concanavalin A (Con A). Following Con A injection (20 mg/kg body weight), greater increases in liver-to-body weight ratio and ALT levels were observed at 12 and 24 hr in rats fed ethanol, compared with control rats fed sucrose. Furthermore, increases in serum interleukin-6 and tumor necrosis factor-alpha levels were noted in ethanol-fed rats, with maximal levels detected at 4 hr declining thereafter, but remaining above control levels at 24 hr. Analysis of T-cell subpopulations showed an increased percentage of CD4+, CD5+, and CD8+ T cells in blood from all groups, but not in liver perfusate. In contrast, a significant increase in the percentage of activated CD25+ T cells was detected in both blood and liver perfusate from rats fed ethanol even 24 hr after Con A injection. When CD4+ and CD8+ T cells from liver perfusate were cultured in the absence or presence of Con A, an increase in interleukin-6 and tumor necrosis factor-alpha production in supernatants was observed in ethanol-fed rats. In cultures stimulated with Con A, a 2- to 8-fold increase in cytokine production was detected, with intrahepatic CD4+ T cells being the major source. Immunohistological analysis revealed infiltration of CD4+ T cells around portal vein and central vein areas associated with fatty liver and severe hepatic necrosis. The results suggest that alcohol consumption induced a dysregulated T-cell population that mediated hepatic necrosis following polyclonal activation with Con A.

Topics: Animals; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Concanavalin A; Female; Liver Cirrhosis, Alcoholic; Liver Cirrhosis, Experimental; Lymphocyte Activation; Lymphocyte Count; Rats; Rats, Wistar; T-Lymphocyte Subsets; T-Lymphocytes

Blood leukocytes of 16 patients with alcoholic liver cirrhosis and 18 healthy controls were induced for interferon (IFN) production by phytohemagglutinin (PHA) and concanavalin A (ConA) in the presence or absence of isoprinosine and levamisole at concentrations of 10 micrograms/ml and 1 ng/ml. This interferon was neutralized in 87-95% by anti-HuIFN-gamma monoclonal antibodies. In the presence of the drugs the IFN-gamma production was enhanced, however, IFN-gamma titers yielded from leukocytes of cirrhotic patients were still below the titers observed in stimulated and unstimulated blood leukocytes of healthy controls. For example, IFN titers induced by PHA in the presence of levamisole (1 ng/ml) in cirrhotic patients were 2.5 times lower (20.2 +/- 11.1 U/ml) in comparison to healthy subjects (50.6 +/- 27.3 U/ml).

Topics: Adjuvants, Immunologic; Adult; Aged; Concanavalin A; Gene Expression Regulation; Humans; Inosine Pranobex; Interferon-gamma; Leukocytes; Levamisole; Liver Cirrhosis, Alcoholic; Lymphocyte Activation; Middle Aged; Phytohemagglutinins

Patients with alcoholic hepatic cirrhosis have a higher predisposition to acquiring infections than healthy individuals, suggesting an alteration in the immune system. They also exhibit an important decrease in certain plasmatic constituents such as zinc, albumin, and transferrin which are involved in the normal immune response. The blastoid transformation of lymphocytes stimulated in vitro with phytohemagglutinin M and P in patients with alcoholic hepatic cirrhosis was studied and the results were correlated with the plasmatic constituents aforementioned. The rate of blastoid transformation was significantly lower (p < .001) in these patients when compared to the control group, but did not correlate directly with the concentration of zinc, albumin, transferrin or circulating globulins. Patients' plasma significantly inhibited the response of normal cells to stimulation with phytohemagglutinin and Concanavalin A; nevertheless, the blastoid transformation of lymphocytes in these patients was not restored to normal levels when incubated with control plasma.

Topics: Adult; Concanavalin A; DNA Replication; Female; Humans; Immunologic Deficiency Syndromes; Liver Cirrhosis, Alcoholic; Lymphocyte Activation; Male; Middle Aged; Phytohemagglutinins; Serum Albumin; Transferrin; Zinc

Concanavalin A-induced lymphocyte proliferation was studied in 25 patients with alcoholic hepatitis or compensated alcoholic cirrhosis. Nine alcoholics without evidence of liver disease were also evaluated. A nonlinear correlation equation, which was natural logarithmic, was applied to individual dose-response proliferation curves and permitted comparisons between patient groups and controls. The proliferative response in all patient groups was significantly lower when compared to healthy controls and was independent of the presence or absence of liver disease. This suggests that some changes in immune function observed in alcoholics may be linked to the direct effects of alcohol on the immune system rather than to the associated liver disease.

Topics: Alcoholism; Concanavalin A; Female; Hepatitis, Alcoholic; Humans; Liver Cirrhosis, Alcoholic; Liver Diseases, Alcoholic; Liver Function Tests; Lymphocyte Activation; Male

Topics: Adult; Concanavalin A; Cytotoxicity, Immunologic; Female; Humans; Immunity, Cellular; Liver Cirrhosis, Alcoholic; Lymphocyte Activation; Male; Middle Aged; Phytohemagglutinins

In order to determine whether or not abnormal suppressor cell function correlates with the absence of a delayed hypersensitivity reaction (DHR) in anergic patients, Con A reactivity and the short-lived suppressor cell activity of peripheral blood lymphocytes (PBL) were studied in 4 groups of patients: (1) Those with peripheral vascular disease (PVD) who reacted with a normal DHR to the intradermal injection of one or more recall antigens; (2) patients with PVD who did not respond with a DHR to any of these antigens; (3) patients with alcohol-related cirrhosis and normal DHR; and (4) cirrhotics who showed no DHR. The data for both short-lived suppressor cell activity and Con A reactivity were not significantly different between anergic patients, patients with normal DHR, and a group of normal controls. Although cirrhotic patients have been reported to show abnormalities in cellular immunity, short-lived suppressor cell activity and Con A reactivity were not significantly different between cirrhotics with normal DHR, PVD patients with normal DHR, and normal controls.

Topics: Concanavalin A; Humans; Hypersensitivity, Delayed; Liver Cirrhosis, Alcoholic; Lymphocyte Activation; Lymphocytes; Male; Skin Tests; T-Lymphocytes, Regulatory; Vascular Diseases

Topics: Adult; Aged; alpha-Fetoproteins; Chronic Disease; Concanavalin A; Female; Ferritins; Hepatitis B; Humans; Liver Cirrhosis; Liver Cirrhosis, Alcoholic; Liver Diseases; Liver Neoplasms; Male; Middle Aged