Depression of lymphocyte reactivity to phytohemagglutinin by serum from patients with liver disease

Abstract

The influence of serum from patients with a variety of liver abnormalities on the in vitro response of normal human peripheral blood lymphocytes to stimulation with phytohemagglutinin was studied. These experiments demonstrate that serum from patients with acute viral hepatitis, chronic Australia antigenemia, common bile duct obstruction, primary biliary cirrhosis, hepatic necrosis secondary to halothane, and alcoholic cirrhosis suppresses DNA synthesis by stimulated normal lymphocytes. Sera obtained from two patients 1 week after surgical correction of their common duct obstruction no longer demonstrated lymphocyte suppression. Dilution of normal serum with serum from either of three patients resulted in more rapid decrease of thymidine uptake by stimulated lymphocytes than when normal serum was diluted with culture medium. This indicates the presence of an inhibitory factor (s) in the patients' sera. No correlation was shown between the extent of thymidine uptake by stimulated lymphocytes and the bilirubin, transaminase, or alkaline phosphatase levels in the serum in which they were cultured. The addition of bile salts to stimulated lymphocyte cultures did result in suppression of the response but only at concentrations much higher than would be expected in serum of the patients studied. Cell death after 72-hr incubation was 42% in normal serum and only 50% in serum from a patient who had demonstrated prominent suppression of DNA synthesis.