Defective interleukin-2 production in children with chronic hepatitis B: role of adherent cells.

Abstract

Chronic hepatitis B (CHB) virus infection is associated with functional abnormalities of cell-mediated immunity, defective interferons alpha and gamma synthesis, and interleukin-2 receptor expression. In this study, interleukin-2 (IL-2) production and the role of adherent cells was evaluated in 25 children chronically infected with hepatitis B virus. IL-2 activity was measured by bioassay in supernatants of phytohemoagglutinin-stimulated peripheral blood mononuclear cells. In a few patients, IL-2 concentration was also immunochemically determined. Coculture experiments using a mixture of adherent cells and lymphocytes from healthy children and patients with CHB were also performed. Children with CHB showed lower IL-2 production than healthy controls. In patients, IL-2 activity was 34.7 +/- 22.5 U/ml as compared to 152.6 +/- 78.5 U/ml of controls. Immunochemical quantitation of IL-2 confirmed a lower IL-2 production in patients. No correlation was found between the functional T-cell defect and the severity of liver damage, degree of viral replication, and duration of the disease. In co-culture experiments, adherent cells from HBsAg-positive patients inhibited IL-2 production following mitogen stimulation of control non-adherent cells by 67%. The inhibitory effect, mediated by patients adherent cells, was abolished by blocking with indomethacin prostaglandins, that are potent local immunomodulators released by adherent cells. Our results further support the observation that in children with CHB virus infection adherent cells play an important role in the inappropriate regulation of immune response, an effect being likely mediated by prostaglandins.