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Differences in the Nature and Kinetics of the Ethanol‐related Circulating Cytotoxic Proteins in Normal Subjects and Patients with Alcohol‐induced Cirrhosis
Author(s) -
Wickramasinghe S. N.,
Clague J. R.,
Barrison I. G.,
Walker J. G.,
Barden G.,
Gardner B.
Publication year - 1989
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.1989.tb00411.x
Subject(s) - cytotoxic t cell , cirrhosis , albumin , ethanol , chemistry , acetaldehyde , alcohol , medicine , endocrinology , serum albumin , biochemistry , in vitro
The kinetics and nature of the nondialyzable cytotoxic activity which appeared in the serum after the consumption of 1.2 g ethyl alcohol per kilogram body weight over 45 min was studied in six healthy volunteers and eight patients with histologically proven alcohol‐related cirrhosis of the liver. Whereas the cytotoxic activity in the dialyzed serum showed a single peak with a maximum value 8 hr after the start of ethanol consumption in the healthy volunteers, it showed two peaks with maximum values at 2 and 8 hr in the patients with cirrhosis. Studies of the fractions obtained by Sephacryl‐S‐300 gel filtration of the 2‐hr postalcohol serum samples revealed substantial cytotoxic activity in the fractions containing both the albumin peak and the IgG peak in the patients with cirrhosis and only in the fractions containing the albumin peak in the healthy volunteers. Experiments with pure IgG preparations obtained from prealcohol and 2‐hr postalcohol sera by chromatography on Q‐Sepharose Fast Flow anion‐exchange resin showed considerable cytotoxic activity in the preparations from the patients with cirrhosis and little or no cytotoxic activity in those from the healthy volunteers. Thus, the early peak of the biphasic serum cytotoxicity curve seen after ethanol consumption by patients with cirrhosis appeared to be caused by the development of a substantial cytotoxic activity in the IgG molecules during the first 2 hr. When prealcohol sera from healthy subjects and patients with cirrhosis were incubated with various concentrations of [ 14 C]acetaldehyde at 37°C for 6 hr, and the reacted sera were dialyzed and subjected to gel filtration, the proportion of radioactivity associated with the IgG peak was found to increase progressively with increasing concentrations of [ 14 C]acetaldehyde. It therefore appeared that the differences in the nature and kinetics of the cytotoxic proteins which circulate after ethanol consumption in healthy subjects and patients with cirrhosis may be due to the generation of higher levels of blood acetaldehyde in the latter. The differences may also be partly related to the increased serum IgG levels and the reduced serum albumin levels often seen in alcohol‐induced cirrhosis.